In its first venture philanthropy deal, FoldRx Pharmaceuticals Inc. signed a five-year collaboration with the nonprofit drug discovery and development arm of the Cystic Fibrosis Foundation, Cystic Fibrosis Foundation Therapeutics Inc. Under the deal, FoldRx could receive up to $22 million to advance new cystic fibrosis drugs.

Richard Labaudiniere, president and CEO of Cambridge, Mass.-based FoldRx, said his company always has been interested in cystic fibrosis because it is the largest disease in which "protein misfolding is linked to the trafficking of protein." He approached CFF after FoldRx's yeast-based screening platform yielded compounds with activity against CFTR, the defective cell membrane protein responsible for the progression of cystic fibrosis.

CFF agreed to provide up to $22 million in milestone-based funding to support preclinical development of two candidates from FoldRx's cystic fibrosis program. FoldRx retains all commercialization and intellectual property rights, although CFF would receive royalties on any products eventually approved. Labaudiniere projected that the program will achieve an investigational new drug application filing in 18-24 months.

Labaudiniere told BioWorld Today that the CFF funding has several advantages over venture capital. In addition to being nondilutive, the funding brings with it access to CFF's network of physicians and expertise in cystic fibrosis.

Venture philanthropy has gained momentum over the past decade as venture capitalists continue to shift their definition of "early stage investments" to later and later-stage projects.

Robert Beall, CFF president and CEO, said his organization recognized that trend and was "a little frustrated" that the knowledge gathered about cystic fibrosis wasn't being translated into new treatments. CFF decided to overhaul its business model, replacing grants to academic institutions with funding for early stage biotechnology projects.

Since 1998, CFF has committed about $250 million in funding to biotechnology companies. Among them are Vertex Pharmaceuticals Inc., which is in Phase II with VX-770; Altus Pharmaceuticals Inc., which is in Phase III with ALTU-135; and PTC Therapeutics Inc., which is in Phase II with PTC124.

Funding from CFF helped all of those companies conduct preclinical work and advance their drugs. (See BioWorld Today, May 9, 2007.)

But funding is not all CFF brings to the table. The organization also offers a network for conducting clinical trials, access to patient tissue samples and assays, and expertise in the cystic fibrosis field, Beall said. Each project funded is supervised by a scientific advisory committee composed of both foundation and company representatives. And the relationship is structured "like a business," he added, although the end goal is not return on investment but delivering products to patients.

The CFF model has inspired other patient advocacy organizations to start their own venture philanthropy efforts, among them the Juvenile Diabetes Research Foundation, the Michael J. Fox Foundation for Parkinson's Research and the Muscular Dystrophy Association.

Prior to the CFF collaboration, FoldRx had raised $59 million in venture capital. That funding has been used to support the company's discovery and development of small molecules to modulate protein misfolding. Often the result of gene mutations, protein misfolding is an underlying cause of many chronic diseases such as Alzheimer's disease, Parkinson's disease, cystic fibrosis and others.

FoldRx's most advanced candidate, Fx-1006A, is designed to stabilize a mutated protein known as transthyretin (TTR) to prevent it from misfolding. The drug is in a Phase II/III trial for the genetic disorder familial amyloid polyneuropathy, and data are expected in 2009. If all goes well, FoldRx expects to file for approval shortly thereafter. (See BioWorld Today, May 30, 2007.)

FoldRx also plans to study Fx-1006A in familial amyloid cardiomyopathy, another condition involving TTR. However, since the disease is not well studied, Labaudiniere said the company is conducting a "natural history study" to follow patients and better understand the natural progression of the disease without introducing Fx-1006A treatment. The data from the study, expected in 2009, will help identify potential endpoints for clinical trials.

Behind Fx-1006A, FoldRx is moving toward in vivo studies with a lead candidate for Parkinson's disease, and Labaudiniere said the company's yeast-based screening platform "will be suitable for Alzheimer's," an indication FoldRx may explore with a partner.

Another company working on protein misfolding is Amicus Therapeutics Inc., of Cranbury, N.J., which raised $75 million in an initial public offering this summer to advance its small-molecule pharmacological chaperones targeting misfolded proteins through late-stage trials in Fabry's disease and Gaucher's disease and midstage trials in Pompe disease. (See BioWorld Today, June 1, 2007.)

Also working in the space are Reata Pharmaceuticals Inc., which uses its RPM (Rescuing Proteins from Misfolding) platform to study protein misfolding, and QRxPharma, which re-engineers existing drugs to take advantage of a gene shown to decrease protein misfolding.