Morphosys: Substanz beginnt sich durchzusetzen

 

Perspektivisch der nächste Sargnagel für rote Zahlen bei ABD serotec.

Gerade für die hochspezifischen Diagnostiker bietet das ingenieursmäßige HuCAL-Baukasten-System für Antikörper doch offensichtlich erheblich Vorteile im Vergleich zu Tierbasierten AKs.

Die ganzen in den letzten Jahren eingerührten Kooperationen werden auch ABD ein lukratives auskommen ermöglichen, auch wenns länger gedauert hat, als ursprünglich erhofft.:

AbD Serotec - Kundeninformation
Martinsried/München und Chelmsford/Essex, UK, 23. September 2008

e2v entwickelt neuartiges Biosensor-System mit HuCAL-Antikörpern von AbD Serotec

AbD Serotec, die Geschäftseinheit für Forschungs- und diagnostische Antikörper der MorphoSys AG, und sein Kunde e2v biosensors, eine Geschäftseinheit der e2v technologies plc, gaben heute ein Forschungsprogramm zur Entwicklung von e2v’s firmeneigenem Biosensor-System Visucare™ bekannt. Das Visucare™-System, eine neuartige Detektionsmethode für die Untersuchung von Biomarkern mit Hilfe eines Einzelantikörper-Immunologietests, kommt in der medizinischen Versorgung in patientennahen, sogenannten Point-of-Care-Untersuchungen bei der Proteinbestimmung zum Einsatz.

e2v biosensors und AbD Serotec begannen im September 2006 e2v’s neuartige Plattform mit AbD’s etablierter Antikörpertechnologie HuCAL zu kombinieren. AbD Serotec hat eine Reihe an spezifisch modifizierten rekombinanten Antikörpern entwickelt, die es e2v ermöglichten, in Machbarkeitsstudien das Wirkungsprinzip ihres Visucare™-Ansatzes zu belegen.

Die Basis der e2v-Technologie bildet die sogenannte Surface Enhanced Resonance Raman Spectroscopy (SERRS), ein elektromagnetisches, oberflächengebundenes Nachweisverfahren. Diese Methode ermöglicht es, die Bindung einzelner Moleküle an eine Silberoberfläche nachzuweisen. Das biomolekulare Schlüsselelement des Visucare™-Ansatzes besteht aus drei Komponenten: einem HuCAL-basierten Antikörper, einem SERRS-Reportermolekül, welches an ein Peptid gebunden ist, und eine Silberoberfläche, an der sich ein elektromagnetisches Feld bildet. Im Ausgangszustand liegt der HuCAL-Antikörper fest gebunden an die Silberoberfläche vor, bindet seinerseits das SERRS-Reportermolekül und hält es so außerhalb des elektromagnetischen Feldes. In Anwesenheit eines Protein-Biomarkers wird das SERRS-Reportermolekül verdrängt, bindet an die Silberoberfläche und verändert messbar das elektromagnetische Feld und somit das SERRS-Signal.

Im Gegensatz zu anderen Systemen benötigt Visucare™ kein Antikörperpaar, um den jeweiligen Biomarker nachzuweisen. Stattdessen benutzt das Verfahren einen einzelnen Antikörper in einem Verdrängungsformat und benötigt deshalb keinerlei Wasch- oder Inkubationsschritte. Damit kann das System ein Ergebnis in weniger als 10 Minuten liefern. Zusätzlich erlaubt das Verfahren die Untersuchung von Biomarkern, die für andere Verfahren nicht zugänglich sind und in nur sehr geringen Mengen vorliegen. e2v biosensors hat eine starke Patentposition gesichert, mit zwei erteilten Patentfamilien und weiteren elf anhängenden Anmeldungen.

“Das Visucare™-System bietet zahlreiche Vorteile im Vergleich zu den derzeit verfügbaren Ansätzen für die patientennahe Untersuchung von Biomarkern, mit Multiplex-Fähigkeit, hoher Sensitivität und Spezifität. Wir etablieren derzeit ein Point-of-Care-Panel an kardiologischen Biomarkern und untersuchen weitere Anwendungen”, kommentiert Dr. Paul Rodgers, CEO von e2v biosensors. “AbD Serotecs Beitrag in Form sehr selektiv bindender rekombinanter Antikörper, die sowohl das zu untersuchende Protein als auch ein davon abgeleitetes Peptid binden können und gentechnisch so modifiziert sind, um an die Silberoberfläche zu binden, waren essentiell für die Etablierung dieses Systems. Wir suchen derzeit nach einem strategischen Partner, um das kommerzielle Potential des Visucare™-Ansatzes in einem breiten Spektrum an Krankheitsuntersuchungen und Point-of-Care-Anwendungen auszunutzen.”

“Die heutige Nachricht belegt erneut die enorme Flexibilität unserer HuCAL-Antikörperplattform und die Vielfalt an möglichen Anwendungsbereichen, die wir anvisieren können. e2v’s Ansatz, eine neuartiges Point-of-Care-Verfahren zu etablieren, ist sehr innovativ und sowohl wissenschaftlich wie kommerziell interessant”, erklärt Dr. Achim Knappik, Leiter R&D von AbD Serotec. „Wir freuen uns, e2v mit Hilfe unserer HuCAL GOLD-Technologie als Quelle für das Schlüsselelement des Visucare™-Ansatzes bei der Etablierung dieses Systems unterstützen zu können.”

Für weitere Informationen besuchen Sie bitte folgenden Link:
http://www.ab-direct.com/about/news_releases-399.html

Meanwhile, other antibody firms have formed lucrative partnerships, such as Tarrytown, N.Y.-based Regeneron Inc., which signed a potential $1 billion discovery and development deal with Sanofi-Aventis Group, of Paris, and Rockville, Md.-based MacroGenics Inc., which secured a deal, also potentially worth $1 billion, with Indianapolis-based Eli Lilly & Co. to develop anti-CD3 antibody teplizumab in Type I diabetes.

Deal-making in the antibody field "has really taken off in the last few years," Rudert said, adding that both mean up-front payments and overall deal volumes are on the rise for antibodies and varying antibody technologies. M&A also is up, "sort of culminating" with Roche Holdings AG's $44 billion offer for Genentech Inc., which has two of the biggest antibody products on the market, Herceptin and blockbuster Avastin (bevacizumab).

Genentech has rejected Roche's offer, though the general consensus is that the deal ultimately will go through, but at a higher price.

And panelists said the hunger for antibodies is not likely to abate any time soon, especially as antibody development and manufacturing capabilities continue to improve.

"It's such a good class of drugs," said Simon Maroney, CEO of MorphoSys AG. "It took so long to iron out all the bugs, but [antibodies] will probably stay popular for at least two to three more decades."

An Inauspicious Beginning

While Herceptin is credited with kicking off the antibody space's success story, it was not the first antibody to gain FDA approval. That distinction goes to Johnson & Johnson's Orthoclone (muromonab), an anti-CD3 antibody developed using a murine antibody technology, which was approved in 1986 for treating organ rejection but failed to make a big splash in the market due in part to its association with serious side effects such as anaphylactic shock, cardiovascular problems and life-threatening episodes of cytokine release syndrome.

The problem, it turned out, was that murine antibody technology had only limited success because there's just too much dissimilarity between mouse and human antibodies, Rudert said.

Chimeric antibody technologies (a combination of mouse and human antibodies) were better, but it wasn't until the development of human antibody technologies that the space began to heat up. And coming down pipelines now are drugs created using antibody-drug conjugate (ADC) technologies, which might prove even more effective.

Beyond that, there are the antibody-drug conjugate technologies - the attachment of a drug to an antibody - which might prove even more effective. Among the most advanced ADC drugs in development is Branford, Conn.-based CuraGen Corp., which last week completed enrollment in a Phase II study of CR011-vcMMAE, a product that comprises a fully human monoclonal antibody against GPNMB that is linked to monomethyl auristatin, a tubulin destabilizing agent, in patients with advanced melanoma.

But, even with the advancements, antibodies still carry a certain amount of development risk.

"A lot of people think antibodies are a slam dunk," said panelist Margaret Karow, executive director of research at Thousand Oaks, Calif.-based Amgen Inc., which markets Vectibix (panitumumab), an anti-EGFR antibody approved in colorectal cancer. "But they are proteins," meaning they come with the same challenges as other protein drugs in development.

They've had their share of safety issues, for one. Cambridge, Mass.-based Biogen Idec Inc.'s multiple sclerosis drug Tysabri (natalizumab, partnered with Dublin, Ireland-based Elan Corp. plc) has been linked to potentially fatal brain disease progressive multifocal leukoencephalopathy, and the FDA recently issued an alert on the increase in serious fungal infections associated with anti-tumor necrosis factor-alpha inhibitor antibodies such as Centocor's Remicade (infliximab). Even worse was the shocking Phase I trial of now-defunct Tegenero AG's TGN1412 antibody that sent six healthy volunteers to intensive care.

Despite those bumps, antibodies have become the fastest-growing drug class, with nearly 1,000 compounds in research and development, many of those in partnership with big pharma.

Pharma "Scrambling" for Antibodies

In one of the largest antibody partnerships to date, German biotech MorphoSys AG signed a massive 10-year discovery and development alliance with Novartis AG that could be worth more than $1 billion, including $600 million that Novartis has committed to pay over the course of the agreement.

Munich, Germany-based MorphoSys picked Novartis after offering the deal, auction-style, to 10 or so top industry players, which just goes to show how far antibody firms have come.

"We started doing business in the mid-1990s when there were no takers," MorphoSys' Maroney told BioWorld Financial Watch. But thanks to the high-profile antibody approvals from Genentech, Centocor and Biogen, antibody products started pulling in significant revenues, and "that's when pharma woke up," he added. Now, he said, marketed antibody drug sales total about $20 billion per year.

MorphoSys's HuCal (Human Combinatorial Antibody Library) technology is a phage display library designed to build up an antibody in a modular fashion. It has been the center of the company's numerous partnerships as well as its own internal pipeline. Alone and with partners, the company has a total of 56 compounds in various stages of development, Maroney said, adding that "our goal is to become an antibody powerhouse."

With the Novartis deal, expected to be the last such collaboration entered by MorphoSys, the firm is assured of a large number of new programs, Maroney said, and the German biotech can "count on about $30 million in free cash flow from the deal over the next 10 years."

That, plus the $200 million currently on its balance sheet, puts the firm "in a happy position to invest in our own pipeline," he said.

MorphoSys' lead drug, MOR103, a fully human HuCAL antibody directed against granulocyte macrophage-colony stimulating factor for treating rheumatoid arthritis, started a Phase I trial in April.

The company, which is staffed by 300 employees and has a market cap of about $500 million, has no interest in becoming one of the antibody firms bought out by big pharma, but that's not to say that pharma won't come knocking.

"We've seen a flurry of acquisitions," Maroney said during the panel discussion. "As the pool of available companies gets smaller, that [interest] will move beyond into the antibody scaffold companies" like Domantis.

"Pharma scrambled to get their hands on those [antibody firms] and now they'll scramble to get their hands on the next-generation [firms]," he added, though he questioned whether M&A is the best solution for the continued development of antibody technology.

"Historically, technology hasn't flourished when absorbed by a pharma firm," he said.

Amgen's Karow agreed, but said pharma firms seem to be learning that "integration sucks the life out of" technology firms and are allowing their acquired companies to operate as separate entities.

AstraZeneca opted to let Gaithersburg, Md.-based MedImmune (plus CAT) continue operating on its own, and the firm serves as the biologics division of AstraZeneca. And Basel, Switzerland-based Roche has promised to let Genentech continue as a separate unit at its South San Francisco-based headquarters if an acquisition gains shareholder approval.

Beverley Carr, director of drug discovery transactions at GSK, said there's an increasing trend for big pharma to buy firms and to keep them intact.

"That's something I can see continuing to happen," she said. "It's what we've done with Domantis and it's worked very well in the short term."

(c) 2008 Thomson BioWorld, All Rights Reserved.

Frühstadium dieser Programme anfallende Kosten werden dabei von
Novartis getragen.

'Die heutige Nachricht markiert einen weiteren wichtigen Schritt bei
der Umsetzung unserer Pläne, unsere firmeneigenen Aktivitäten in der
Medikamentenentwicklung auszubauen. Dies ist für MorphoSys eine
großartige Gelegenheit, gemeinsam mit Novartis bei der Entwicklung
eines Antikörpers gegen ein sehr vielversprechendes Zielmolekül
mitzuwirken', sagte Dr. Simon Moroney, Vorstandsvorsitzender der
MorphoSys AG. 'Wir sehen diese Entwicklungsoptionen als eine sehr
wertvolle Komponente unserer Vereinbarung mit Novartis an. Sie geben
uns die Möglichkeit, unsere Fähigkeiten in der
Medikamentenentwicklung in Verbindung mit einem der erfolgreichsten
und erfahrensten Unternehmen der pharmazeutischen Industrie
auszubauen.'

Für weitere Informationen kontaktieren Sie bitte: Dr. Claudia
Gutjahr-Löser, Head of Corporate Communications & Investor Relations,
Tel: +49 (0) 89 / 899 27-122, gutjahr-loeser@morphosys.com oder Mario
Brkulj, Manager Corporate Communications & Investor Relations, Tel:
+49 (0) 89 / 899 27-454, brkulj@morphosys.com.