Theravance Biopharma has announced that its Phase 3 CYPRESS study of ampreloxetine in patients with symptomatic neurogenic orthostatic hypotension (nOH) due to multiple system atrophy (MSA) failed to meet its primary endpoint.
The study’s Orthostatic Hypotension Symptom Assessment (OHSA) composite score showed no statistically significant improvement, prompting the company to wind down the ampreloxetine program.
In response, the company’s Strategic Review Committee is accelerating its evaluation of options to maximize shareholder value, including a potential sale of the company. “The Committee will act with urgency to evaluate a broad range of value maximizing and tax efficient alternatives, including but not limited to a sale of the company,” Theravance said, noting there is no guarantee the process will result in a transaction.
Theravance is also undertaking an organizational restructuring to align resources with its commercial focus on YUPELRI. The plan involves winding down R&D and significantly reducing G&A functions, expected to cut operating expenses by roughly 60% from 2025 levels of $110 million. Full cost savings of approximately $70 million are projected to materialize by Q3 2026.
These changes, combined with continued YUPELRI sales, are expected to generate $60–70 million in annualized cash flow starting in Q3 2026. This includes $45–55 million of income from operations (excluding non-cash share-based compensation) and projected interest and other income, not accounting for a potential $100 million TRELEGY milestone.
Following the ampreloxetine decision, Theravance’s key assets include an expected $400 million cash balance at the end of Q1 2026, a 35% interest in YUPELRI producing durable cash flow, potential TRELEGY milestone payments, and Irish tax attributes.
“We are disappointed that ampreloxetine did not meet the primary endpoint in the CYPRESS study. These results are particularly disheartening for the patients who are suffering from this rare disease and were hoping for a new treatment option and for the employees who dedicated years of work to this program. I want to sincerely thank the patients, caregivers, investigators, and our team for their commitment and contributions to this effort,” said Rick E Winningham, Chief Executive Officer of Theravance Biopharma.
“Given these results, we are taking decisive steps to restructure the organization and significantly reduce our cost base, which we expect will allow YUPELRI to drive meaningful and sustainable cash flow for the company. With a profitable commercial product, an expected cash balance of approximately $400 million at the end of the first quarter of 2026, and the anticipated $100 million TRELEGY milestone in 2026, we continue to have a strong set of assets.”
“Consistent with our commitment to act in the best interests of the Company and its shareholders, and alongside the organizational restructuring actions we announced today, the Strategic Review Committee is accelerating its ongoing evaluation of value maximizing strategic alternatives,” said Susannah Gray, independent Chair of the Board and Chair of the Strategic Review Committee.
“The Committee was established with a clear mandate to deliver maximum value to Theravance Biopharma shareholders, and over the last year and a half, has been actively engaged in overseeing that the Company's strategy delivers on this objective, including with the $225 million sale of our remaining royalty interest in TRELEGY in 2025.
"Today, Theravance Biopharma has a cash-generative commercial asset, strong balance sheet and sizable near-term milestone payout opportunity, and the Committee is squarely focused on acting with urgency and discipline to ensure that we achieve the best outcome for shareholders.”
