Bristol-Myers Squibb Co. (BMS) inked a pair of separate deals that could be worth more than $1 billion if both pan out fully, though the one with Biogen Inc. licensing BMS-986168 gained more buzz than the pact with Roche Holding AG for BMS-986089.
Biogen, of Cambridge, Mass., is doubling down in the tau space by bringing the BMS antibody aboard to accompany BIIB-076, already in-house, and the company could have a leg up not only in progressive supranuclear palsy (PSP) but in Alzheimer's disease (AD) as well, Jefferies analyst Brian Abrahams wrote in a research note. "The antibody is a humanized IgG4k [drug] originally developed by Ipierian Inc.," of South San Francisco, he noted, which New York-based BMS bought in 2014. "Some safety and efficacy (pharmacokinetics/immunogenicity) data already exist for the antibody. It was tested in a phase I, single-center/single-ascending-dose trial in 64 healthy volunteers who received one infusion and were followed up to eight months post-infusion. Though it does not appear there are any patient data publicly available, Biogen noted [its] encouragement over efficacy data, indicating the company likely was privy to at least interim results from an ongoing phase I study in 48 patients with PSP," he wrote. Biogen's BIIB-076 was discovered by Schlieren, Switzerland-based Neurimmune Holding AG and is undergoing a phase I trial in healthy volunteers and some AD patients. (See BioWorld Today, April 30, 2014.)
Under the terms, Biogen is forking over $300 million with potential milestone payments of up to $410 million and will assume the remaining obligations to former stockholders of Ipierian related to the BMS buyout. Clinicaltrials.gov describes a phase II trial in PSP, and Biogen said BMS-986168 will enter a phase II AD study soon. The PSP experiment is expected to enroll 396 subjects, and the primary outcome is change in PSP rating scale from baseline up to 52 weeks as well as frequency of adverse events. Patients would receive an intravenous infusion of BMS-986168 or placebo on specified days.
"There are some interesting preclinical data showing that human AD induced pluripotent stem cells (Ipierian was founded on pluripotent stem cell technology) can secrete novel tau fragments that can be internalized by recipient neurons and can induce dysfunction," analyst Abrahams wrote. "Therefore, the secreted extracellular tau (etau) may have some pathogenic properties. Notably, though most anti-tau antibodies are designed to bind to the full-length protein, BMS-986168 can bind to the secreted etau form and may enable successful removal of the toxic form of the protein that could attenuate disease progression, including the development of deposits or neuronal tangles." It's an idea similar to that behind Biogen's aducanumab and anti-amyloid beta antibodies.
Evercore ISI analyst Umer Raffat, in an email alert to investors, said the "next key readout for this program is mid-2019 [and] this will be an important de-risking event for this program. If [the drug] 'works,' market opportunity is sizable (perhaps $2 billion worldwide), but we did notice Abbvie Inc. has an ongoing phase II with an anti-tau [candidate] also in this same indication and similar timelines."
In January, North Chicago-based Abbvie started two phase II programs with ABBV-8E12 in patients with early AD and PSP. The FDA has granted fast-track designation for the compound, and U.S. regulators as well as the EMA gave the candidate orphan drug designation. ABBV-8E12 came from Washington University spinout C2N Diagnostics LLC, of St. Louis. (See BioWorld Today, Sept. 12, 2016.)
The tau hypothesis got much airtime at last August's Alzheimer's Association International Conference in Toronto, shortly after Singapore-based Taurx Pharmaceuticals Ltd. reported a phase III blowup with tau aggregation blocker LMTX. Used along with the standard, modestly beneficial AD drugs, the candidate added no value.
In an Aug. 8 report, H.C. Wainwright analyst Andrew Fein said Taurx's bad luck did "not have read-through to tau as a target," and he highlighted Abbvie's prospect as well as the BMS compound that was just licensed to Biogen. "A body of longitudinal data supports that tau pathology closely correlates with neurodegeneration and onset of clinical dementia, with dynamic changes in tau pathology still evident during mild cognitive impairment," he wrote, adding that amyloid beta "has plateaued by the time clinical symptoms are evident. The observation that tau appears to spread trans-synaptically, propagating in a prion-like fashion between neurons and interconnected brain regions, has been gaining traction."
The other BMS deal, licensing out BMS-986089 – an anti-myostatin adnectin in early development for Duchenne muscular dystrophy – has Basel, Switzerland-based Roche paying $170 million with another $205 million promised if goals are met. BMS gained that drug by way of a buyout, too: the 2007 deal to take over Adnexus Inc., of Waltham, Mass., for $430 million. Adnexus had filed for an IPO worth at least $86 million but opted for the BMS exit instead. (See BioWorld Today, Aug. 23, 2007, and Sept. 25, 2007.)
BMS has enough to keep itself busy, including what spokeswoman Christina Trank described as "a diverse early portfolio of immuno-oncology mechanisms that we are evaluating across a broad range of disease areas and modalities," with 11 molecules in the clinic. Antifibrotics are in the works as well, with focus on advanced NASH and NASH-caused cirrhosis, plus idiopathic pulmonary fibrosis. In autoimmune disorders, research is taking aim at rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease.
"In particular, we hope to generate data potentially for TYK2 and BTK [inhibitors, both in phase II] during the year," she told BioWorld Today. Cardiovascular research is focused on heart failure and thrombosis. Several candidates are in development that could have a "transformational impact," including the nitroxyl-donor asset brought aboard in the late-2015 potential $1.7 billion-plus takeover of Chapel Hill, N.C.-based Cardioxyl Pharmaceuticals Inc., which has been advanced into phase IIb trials. (See BioWorld Today, Nov. 3, 2015.)