Small-molecule mRNA translation expert Anima Biotech Inc. has landed a significant new preclinical research deal with Takeda Pharmaceutical Co. Ltd., covering as many as six programs for genetically defined neurological diseases. The deal starts with $120 million in up-front and preclinical research milestone payments for Anima, but altogether the two-part collaboration could hold as much as $2.3 billion in clinical and commercial milestone payouts for the company, providing substantial support for its internal pipeline, Anima co-founder and CEO Yochi Slonim told BioWorld.

Takeda has taken an initial interest in both Anima's discovery-stage Huntington disease (HD) program and small molecules for up to two additional targets. Assuming success, milestone payments to the Tel Aviv, Israel-based company for the programs could reach $1.1 billion. Takeda, Japan's third biggest pharma company by market cap, has also agreed to a time-limited option to expand the collaboration with up to three additional targets, which could hold up to $1.2 billion in additional milestone rewards for Anima. Takeda would pay tiered royalties on any successful products of the work.

The agreement is privately held Anima's second big pharma partnership after landing a multiyear deal with Eli Lilly and Co. to develop translation inhibitors for selected neuroscience targets in July 2018. As with that deal, the Takeda agreement will see Anima use its Translation Control Therapeutics platform to discover new molecules capable of controlling the translation of mRNA into proteins. Together, the partners will work to get the molecules to the clinic, with Takeda taking things from there as it advances with exclusive rights to develop and commercialize all assets included in the deal.

Though there were other contenders seeking to partner on the HD program, Slonim said he was looking for one with more than just an ability to handle the heavy lift of clinical trials. Takeda is pursuing that field with a very strong focus and already had a lot of expertise in the space from having done other deals, he said.

How the deal fits with Takeda's most pertinent other deal, its February 2018 tie-up with Wave Life Sciences Ltd. on oligonucleotide therapeutics for CNS disorders, is unclear. That agreement committed up to $230 million in cash to Wave in exchange for Takeda securing options to co-develop and co-commercialize Wave’s CNS development programs in HD, amyotrophic lateral sclerosis and frontotemporal dementia, as well as its discovery-stage program targeting ATXN3 for the treatment of spinocerebellar ataxia 3.

In its most recent business update, March 4, Wave said it’s using its new backbone chemistry modifications to design stereopure oligonucleotides for indications such as Alzheimer’s and Parkinson’s disease as part of its Takeda collaboration. However, a hitch with its U.S. clinical HD program may explain part of Takeda's interest in other options for the indication.

Though placebo-controlled phase Ib/IIa trials evaluating the safety and tolerability of intrathecal doses of Wave's HD candidates are underway outside the U.S., the company has faced a challenge with the U.S. studies. The FDA won’t allow it to progress to the multiple ascending-dose portions of the trials in the U.S. unless its team conducts an additional preclinical study and presents it to the agency for its review. Furthermore, for the single-dose portion of the first of the trials in the U.S., escalation to its highest proposed doses is subject to the FDA’s review and approval of additional monitoring plans.

That said, Wave’s team said it still expects to deliver readouts from both its ex-U.S. Precision-HD1 and Precision-HD2 trials of WVE-120101 and WVE-120102, respectively, at the end of the first quarter. Furthermore, this year, Wave is planning to start dosing in a new trial of WVE-003, a newer HD candidate using the company’s improved backbone chemistry modifications.

The small-molecule difference

Despite long-running efforts to develop mRNA therapies, a number of challenges have faced the endeavor. Summed up by University of Copenhagen researchers last year in Pharmaceutics, those challenges include the large size of mRNA molecules, their intrinsic instability and tendency toward degradation by nucleases, and mRNA's activation of the immune system.

A small-molecule approach to mRNA makes a big difference, Slonim said. "This is coming back to where the whole pharmaceutical industry has expertise, and capabilities in distribution and manufacturing," he said.

Much like HD programs at Wave and Ionis Pharmaceuticals, which has partnered with Roche Holding AG on the phase III antisense candidate tominersen for HD, Anima is reducing the production of the toxic mutant huntingtin protein. Unlike those programs though, Anima's small-molecule approach could enable oral delivery of a drug with that capacity.

As it moves forward, Anima is applying its platform to a broad array of indications, led by its lung fibrosis program targeting Collagen-1 translation inhibitors, now less than a year away from the clinic, and a lead oncology program focused on c-Myc, a major oncogene that acts as a transcription factor. Financed by private investors, Anima employs about 70 people.

One of the company's most high-profile competitors might be Arrakis Therapeutics Inc., which last year inked a multibillion dollar deal of its own with Roche. Adjacent work is also underway at Ribometrix Inc., which landed its own $1 billion-plus deal with Roche in January.