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Asceneuron Latest Ascension from Merck's Geneva Ashes

By Marie Powers
Staff Writer

The third spin-off from the entrepreneurship partnership program (EPP) launched in April by Merck KGaA biopharmaceutical division Merck Serono SA in conjunction with the closure of its Geneva headquarters, Asceneuron SA is focusing on one of biotech's most elusive targets: Alzheimer's disease (AD).

Launched in October with €5 million (US$6.4 million) in seed funding from Merck Serono, Asceneuron is seeking to advance Merck Serono's preclinical programs in AD and tau protein-related pathologies into the clinic on an accelerated timetable, according to Frank Armstrong, a former R&D executive with tenure at Merck Serono, AstraZeneca plc and Bayer AG who serves as Asceneuron's co-founder and executive chairman.

Other co-founders are Dirk Beher, chief scientific officer, who served as director of the Merck Serono unit specializing in AD and Parkinson's disease (PD) neurobiology and in vitro pharmacology, and Christoph Wiessner, head of discovery, who directed the PD/AD1 in vivo pharmacology unit at Merck Serono and previously headed Novartis AG's central nervous system target and lead discovery unit.

Merck Serono Ventures is managing the investment and has representation on the company's board of directors.

Based in Lausanne, Switzerland, Asceneuron employed eight Merck Serono employees to move its AD programs from lead optimization to Phase I studies, where the start-up plans to seek partnering and licensing opportunities.

The company's name – derived from a contraction of "ascending neuron" – is designed to reflect not only its therapeutic targets and but also the founders' aspirations for Asceneuron to become a rising star in the AD field.

Rather than concentrating on a single platform, the company's initial approach is to pursue three complementary Merck Serono drug discovery programs covering a range of mechanisms and clinical targets, from symptomatic relief to disease modification, Armstrong explained. Asceneuron's undisclosed small molecules are well characterized, designed to improve cognitive function and target toxic tau protein and amyloid-beta peptides by modulating molecular pathways known to be involved in memory loss and its neuropathology.

"We don't have them prioritized," Armstrong told BioWorld Today. "They're at slightly different stages of preclinical development."

He declined to speculate how quickly one of the programs may advance into human studies.

Although Asceneuron has the resources to develop the programs in parallel, the program focused on symptomatic treatment has a cognitive effect that is likely to offer an early proof-of-concept signal, added Roel Bulthuis, head of Merck Serono Ventures.

"We'll focus on getting that proof of concept out so we can use that data in further financing discussions," Bulthuis said.

Failures in pivotal AD studies have been among the biggest disappointments in biotech this year. Among them were the Phase III miss of Eli Lilly and Co.'s candidate solanezumab in mild-to-moderate AD and multiple Phase III fiascos in Pfizer Inc. and Johnson & Johnson's bapineuzumab, originally discovered and developed by Elan Corp. plc. (See BioWorld Today, Aug. 8, 2012, and Aug. 27, 2012.)

Cancellation of bapi's program led Elan to spin out its early stage neurology assets into the drug discovery firm Neotope Biosciences, which also is investigating the role of tau in AD. (See BioWorld Today, Aug. 14, 2012.)

"We recognize it's a difficult area for research and it's a difficult area for clinical development," Armstrong admitted. "But we also recognize that the opportunity that exists is very substantial. We have a range of clinical targets and a range of different sorts of products we're pursuing. We obviously believe that we can learn from some of the successes and some of the problems in Alzheimer's disease and follow a clinical development path which generates from encouraging data."

A key strategic advantage for Asceneuron is that Merck Serono made significant investments in the AD programs under the aegis of the company's co-founders.

"We've worked to get a portfolio of programs together that target very distinct mechanisms of action in Alzheimer's disease," Bulthuis told BioWorld Today. "We believe that we have a great chance in terms of translating the preclinical work that was done into clinical success, and we see a very clear path forward with that."

Merck Serono's decision to discontinue the work had nothing to do with the quality of the program, he added, resulting simply from a strategic planning decision within Merck, which owns no rights or options to the molecules.

Asceneuron follows the creation in August of Prexton Therapeutics, formed around Merck Serono's R&D portfolio in PD to pursue programs targeting the metabotropic glutamate receptors mGluR3 and mGluR4, and the formation in September of Quartz Bio, a biomarker data management and analysis service.

Asceneuron attracted the lion's share of financing, to date, from the EPP efforts – more than twice the seed funding of the other two spin-offs.

"We wanted to fund this company to have the resources to execute its business plan, whether or not we're able to attract external financing," Bulthuis said.

The EPP is part of a €30 million commitment aimed at reducing the impact on local employment following the transfer of Merck Serono's headquarters from Geneva to Darmstadt, Germany, earlier this year and the closure of Merck's R&D operations in Switzerland. (See BioWorld Today, June 20, 2012.)