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Plexxikon Rejoins with Roche in $335M Deal for Raf Inhibitors
(BioWorld Today Via Acquire Media NewsEdge) Plexxikon Inc. and Swiss drugmaker F. Hoffmann-La Roche Ltd. have signed another deal for a Raf kinase inhibitor, this time for PLX5568, a potential treatment for a genetic kidney disease that also might work as a painkiller.
The deal, worth about $335 million over the term of the partnership, calls for a $60 million up-front payment to Plexxikon. The up-front money is expected to extend the company's cash runway through early 2012, Kathleen Sereda Glaub, president of Plexxikon, told BioWorld Today. She said the company is in a good financial position and indicated that Plexxikon will not have significant funding obligations going forward under the deal with Roche.
Plexxikon and Roche plan to co-develop PLX5568 and any other products that arise under the collaboration through commercialization. Currently, PLX5568 is in a Phase I study in healthy volunteers. Berkeley, Calif.-based Plexxikon is responsible for development of the product through the completion of that trial.
Clinical development is set to transition to Roche with the start of Phase II trials, which are expected to be initiated in the target population later this year. PLX5568 is designed as an oral treatment for polycystic kidney disease, a genetic disease that can lead to the loss of kidney function and may require dialysis or transplantation in some cases.
The agreement also covers development of any additional selective Raf inhibitors for other diseases. The compound has been studied in preclinical models for acute, inflammatory and neuropathic pain, and Roche and Plexxikon may explore further testing in human clinical trials of PLX5568 for pain.
Plexxikon would be eligible to receive further payments based on the successful achievement of milestones for other compounds and indications. The company also would receive royalties for any sales related to products under the collaboration. Plexxikon retains an option to co-promote PLX5568 or any other product resulting from the collaboration for any non-PKD indication in the U.S.
PKD is estimated to affect more than 600,000 patients in the U.S. It is a genetic disease in which cysts form in the kidneys and become so enlarged that they cause the loss of kidney function in most patients.
The disease, which has two forms - PKD 1 and 2 - typically manifests as severe hypertension in adults in their 20s. Hypertension can be managed in those patients with existing medications; however, no treatments are available for the underlying disease of PKD. Many patients with the disease end up on dialysis later in life or require transplantation.
But Plexxikon hopes that its compound will work to slow the formation of the cysts in PKD patients, possibly delay the start of dialysis in those patients or avoid the need for dialysis altogether. In orthologous models (the closest thing to human models) of both genetic forms of PKD, PLX5568 has been shown to decrease cyst size and improve kidney function. And nonclinical toxicology studies have confirmed the expected safety profile of the drug.
This is the second collaboration between the two firms, the first of which began in 2006. The 2006 agreement covers PLX4032, a potential targeted cancer therapy designed to selectively inhibit a mutation in the B-Raf kinase gene found in about 70 percent of malignant melanomas, as well as a large number of colorectal and thyroid cancers.
In exchange for exclusive worldwide rights to PLX4032 and other compounds targeting the B-Raf mutation, Roche paid Plexxikon $40 million up front and agreed to provide $6 million in research funding for two years. The oncology compound currently is in a Phase I trial. The total worth of the 2006 collaboration agreement is a potential $706 million. (See BioWorld Today, Oct. 5, 2006.)
The company has an investigational treatment for diabetes (PLX204), the IND for which was returned by Wyeth. Plexxikon hopes to meet with the FDA to lay out the clinical development for that product, which acts on the peroxisome proliferator-activated receptor, and talk to potential partners later this year.
In addition, Plexxikon has a preclinical program to develop an oral kinase inhibitor for rheumatoid arthritis (RA) and other autoimmune diseases (PLX 3397). More recent RA treatments all have been injectable drugs. Plexxikon hopes to file an IND in early 2009 for its first-in-class oral disease modifying antirheumatic drug for RA and other autoimmune diseases.
K. Peter Hirth, CEO of Plexxikon, told BioWorld Today that the company's drug discovery platform is "living up to its promise and keeps cranking out" compounds that may serve unmeet medical needs. He contrasted Plexxikon's kinases with others in development, saying that one of the company's hallmarks is its ability to make what appears to be "very clean and safe kinase inhibitors." Hirth noted that most kinase inhibitors are in oncology, an area where the tolerance for side effects is much higher. But kinase inhibitors will have to have much cleaner safety profiles if they are to be used in more chronic diseases that are not life threatening, he said.
And that is where he said he believes Plexxikon stands apart, with its highly selective kinases that have a different binding site than other kinases and appears to avoid some of the cross-reactivity of other kinase inhibitors. n
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