In a bid to expand its presence in CNS to a wider range of neurodegenerative diseases following a substantial restructuring last month, Alkermes plc has moved to acquire privately held neuronal epigenetics specialist Rodin Therapeutics Inc. for $100 million up front and up to $850 million in clinical, regulatory and commercial milestones. Alkermes said it intends to advance IND-enabling activities for Rodin's lead preclinical assets, prioritizing those ahead of future clinical development of Rodin's initial clinical candidate, the histone deacetylase inhibitor (HDAC) RDN-929.

Alkermes shares (NASDAQ:ALKS) fell 4% to $20.16 on Monday, down from a 52-week high of $37.75, reflecting in part disappointment over its failure to secure approval for a major depressive disorder therapy and other challenges. The company's top products are its alcohol dependence drug, Vivitrol (naltrexone), and the schizophrenia drug Aristada (aripiprazole lauroxil).

Rodin's work has focused on selective inhibition of the HDAC?co-repressor of repressor element-1 silencing transcription factor (CoREST) complex. Since its co-founding by Atlas Venture and funding by Atlas and other high-profile VCs, it has sought to develop multiple programs, moving ahead after termination of a valuable deal with Biogen Inc. (See BioWorld, Sept. 19, 2017.)

Data from evaluations of Rodin's candidates in multiple preclinical models showed that inhibition of the HDAC-CoREST complex resulted in increased spine density and synaptic proteins, an important outcome supporting Alkermes' goals, which CEO Richard Pops said include "building on our broad experience in psychiatry."

Blair Jackson, senior vice president of corporate planning, Alkermes

There have been a lot of data demonstrating that lower neuronal density correlates with cognitive declines, Blair Jackson, Alkermes' senior vice president of corporate planning, told BioWorld. The theory is that "if you can increase your neuronal density, you can enhance potential cognitive outcomes. The same goes as you get into other areas, whether it's Huntington's disease or depression or a number of different neurodegenerative states," he said.

Acquisition of Rodin by Alkermes, beyond the share movement, was mixed. SVB Leerink analyst Marc Goodman said it was good to see Alkermes "finally" using business development to improve its pipeline, while acknowledging the assets added were too early stage to value. "In Rodin's collection of finely tuned HDAC-targeting molecules, Alkermes would like to find the asset that minimizes the hematoxicity which has been observed in the current HDAC assets that are approved," he said.

Evercore ISI analyst Umer Raffat was concerned with more fundamental aspects of the deal, which he said raised "more questions than answers," especially in light of the relatively low up-front for a VC-backed company holding a phase Ib asset already tested in Alzheimer's disease.

Jackson, however, had a straightforward explanation for the deal. Discussions between the teams at Alkermes and Rodin, going back at least a couple years, revealed that they had "a really elegant solution" to addressing the neuronal density issue, Jackson said. Today, Rodin's chemistry and the biological understanding around it "has really reached a point where we can start to exploit it within the clinic," he said. "Biogen's loss is our gain."

Despite the ribbing, presumably Biogen and Alkermes retain strong ties, not least of all related to their joint development of the new multiple sclerosis therapy Vumerity (diroximel fumarate) and partnership around Ampyra (dalfampridine)/Fampyra (fampridine).

Alkermes said it plans to continue Rodin's preclinical research program focused on the subset of frontotemporal dementia patients with an inherited mutation of the progranulin gene called FTD-GRN, an indication already in the crosshairs of another Atlas-funded company, Arkuda Therapeutics. (See BioWorld, Nov. 8, 2019.)

Alkermes will also pursue exploratory work in hematological disorders and oncology, it said, noting that it would incur about $20 million of incremental R&D expenses in 2020 related to the advancement of Rodin's development candidates. Rodin has at least two preclinical molecules in its portfolio focused on sickle cell disease and at least another two oncology compounds designed to inhibit growth in neuroblastoma cell lines.

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