SEATTLE—Attracted by a portfolio of small-molecule compoundsfor the treatment of cancer and inflammatory diseases—and continuing its pathtoward broadening its oncology portfolio—Gilead Sciences Inc. in late Februarysigned an agreement to acquire Calistoga Pharmaceuticals Inc., a privately heldbiotechnology company, for $375 million.
Gilead is funding the acquisition, which is expected toclose in the second quarter pending regulatory approval and customary closingconditions, through available cash on hand. Gilead—which is based in FosterCity, Calif., but also has operations in Seattle, where Calistoga operates—willalso pay Calistoga up to an additional $225 million if certain milestones areachieved.
With a portfolio of compounds that selectively targetisoforms of phosphoinositide-3 kinase (PI3K)—the pathway shown to be a centralsignaling pathway for cellular proliferation, survival andtrafficking—Calistoga's lead product candidate is CAL-101, a first-in-classspecific inhibitor of the PI3K delta isoform.
Four isoforms of the PI3K have been identified: alpha, beta,delta and gamma. The differentiated function and cellular expression of each ofthese PI3K isoforms offers an opportunity to develop novel therapeutics.Targeting specific isoforms may offer a more selective treatment approach, withthe potential to result in an improved efficacy and safety profile, saysCalistoga.
CAL-101 is a delta-selective PI3K inhibitor being evaluatedfor the treatment of hematologic malignancies. PI3K delta is preferentiallyexpressed in leukocytes involved in a variety of inflammatory and autoimmunediseases and hematological cancers. CAL-101 is currently in Phase II studies asa single agent in patients with refractory indolent non-Hodgkin's lymphoma(iNHL) and in combination with rituximab in treatment-naive elderly patientswith chronic lymphocytic leukemia (CLL).
"Our team at Calistoga Pharmaceuticals was the first todemonstrate the clinical benefit of targeting the delta isoform of PI3K as anovel treatment approach for patients with CLL and iNHL," explains CarolGallagher, Calistoga's president and CEO. "We are pleased to join Gilead,as they share our vision that more targeted therapies have the potential toimprove the lives of patients with cancer and inflammatory diseases."
According to Dr. Norbert W. Bischofberger, Gilead'sexecutive vice president of R&D and chief scientific officer, the purchaseof Calistoga builds on the company's recent acquisitions of CGI Pharmaceuticalsand Arresto Biosciences, and serves to further broaden Gilead's pipeline andexpertise in the areas of oncology and inflammation. Nathan Kaiser, a spokesmanfor Gilead, notes that the Arresto acquisition in particular gave Gilead PhaseI studies of GS 6624 in solid tumors and in idiopathic pulmonary fibrosis.
"Cancer remains an area of significant unmet medical need,and our increased understanding of the genetic basis of cancer allows for thedevelopment of disease-specific targeted therapies," Kaiser says. "We are veryencouraged by emerging clinical data for CAL-101, and this compound couldrepresent an advance for the treatment of certain hematological cancers."
Kaiser adds that Gilead may pursue additional purchases withlike-minded companies.
"We remain interested in pursuing additional opportunitiesto acquire companies, drugs or technologies that have the potential to augmentor complement our therapeutic areas of focus," he says. "We remain focused onassets with products in Phase I or II, but as always, we reserve the right tobe opportunistic, if the asset makes sense."
Calistoga is also working on other selective PI3K inhibitorsthat are in preclinical development, and may have application in both oncologyand inflammatory diseases.
Following the closing of the acquisition, Calistoga's 20employees will work out of Gilead's Seattle facilities, Kaiser says.
A venture-backed company, Calistoga's top-tier investorsinclude Alta Partners, Amgen Ventures, Frazier Healthcare, Latterell VenturePartners, Quogue Capital and Three Arch Partners.