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As Ambit Eyes IPO, Astellas Drops FLT3 Partnership

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By Marie Powers
Staff Writer

Astellas Pharma Inc. dropped the hammer on Ambit Biosciences Corp., ending its collaboration on the joint development and commercialization of FMS-like tyrosine kinase-3 (FLT3) inhibitors, including lead program quizartinib (formerly AC220), effective Sept. 3.

Astellas exercised its right to terminate the program as part of the worldwide license agreement inked with Ambit in 2009. (See BioWorld Today, Dec. 21, 2009.)

Over the next six months, the companies will work together to transfer management of ongoing clinical trials and their governing investigational new drug applications to Ambit, which will then regain all rights to the quizartinib clinical trial and development program.

However, the timing couldn't be worse for San Diego-based Ambit, which last month filed an S-1 with the SEC seeking to raise up to $57.5 million in a proposed initial public offering (IPO), with the funds used to continue development of quizartinib. (See BioWorld Today, Feb. 22, 2013.)

The S-1 also indicated that existing stockholders had agreed to purchase additional shares at the public offering price in a separate private placement.

Though total proceeds remain undisclosed, the raise was designed to fund Ambit for at least 12 months, through receipt of top-line data from a planned Phase III trial of quizartinib in relapsed/refractory acute myeloid leukemia (AML) and ongoing Phase I trials of the drug in combination with chemotherapy for front-line therapy and maintenance therapy following hematopoietic stem cell transplantation (HSCT).

How the amount or timing of the IPO as well as the private placement might be affected by dissolution of the Astellas partnership remain open questions. Citing the company's quiet period, Ambit spokesman David Schull referred to a statement issued jointly by the companies quoting Michael Martino, Ambit's president and CEO, as "fully committed" to executing the Phase III trial as planned and advancing quizartinib toward approval.

"With the Phase II study results for quizartinib that were presented at the ASH [American Society of Hematology] annual meeting last December, we and members of the medical community continue to be excited about quizartinib and its potential to meet a significant, unmet need in AML patients," Martino said.

Phase II data on quizartinib suggested three key clinical benefits: a high response rate as monotherapy in relapsed/refractory FLT3 ITD-positive patients, a substantial number of patients bridged to HSCT and improved overall survival of those patients compared to historical data. (See BioWorld Today, Dec. 11, 2012.)

"Ambit believes the compelling data increase the value of quizartinib," Schull told BioWorld Today.

Although Astellas has overseen the Phase IIb study and two Phase I trials of quizartinib, Ambit and Astellas worked closely throughout the collaboration, Schull added. In addition to the Phase I and II trials that Ambit conducted involving more than 400 patients, company executives had good insight into the trials managed by Astellas through active participation in joint development committee meetings, he said.

Indeed, Ambit raised $50 million in November 2012 on the strength of the quizartinib Phase II data, despite the fact that an earlier, less specific candidate from Cephalon Inc. blew up in late-stage AML trials in summer 2009.

Ambit's Martino had described that compound, lestaurtinib, as "a fairly dirty kinase inhibitor" that hit more kinases than FLT3. But Novartis AG, of Basel, Switzerland, had PKC412, a multikinase inhibitor with FLT3 activity that also failed in a Phase III combo trial. Cambridge, Mass.-based Millennium Pharmaceuticals Inc., now a unit of Japan's Takeda Pharmaceutical Co. Ltd., didn't make it with MLN518, either.

Still, "game changer" quizartinib is specific, long-lasting and relatively safe, Martino had said. (See BioWorld Today, Nov. 7, 2012.)

For its part, Astellas simply cited "strategic reasons" for its decision to drop the FLT3 program and reaffirmed its commitment to the oncology space.

Officials at the Tokyo-based big pharma could not be reached for comment.

FLT3 inhibitors represent "an interesting approach" in AML, said David D. Miller, CEO of the independent research firm Biotech Stock Research LLC. Hematologists are accustomed to using targeted therapies, "and they're always looking for new ones to add to their armitarium," he noted. While acknowledging he's not a FLT3 specialist, Miller added that Ambit's data at ASH "seemed promising."

In addition to quizartinib, Ambit's clinical pipeline includes AC410, an oral JAK2 inhibitor, and CEP-32496, a BRAF inhibitor licensed to Teva Pharmaceutical Industries Ltd. Ambit's preclinical portfolio includes a CSF1R inhibitor program.