Category: 3. Business

• YUPELRI^® net sales reached an all-time high of $71.4 million, recognized by Viatris, up 15% year-over-year ¹ , and achieved record brand profitability
• Open-label portion of the pivotal Phase 3 CYPRESS study of ampreloxetine now complete; topline readout on track for Q1 2026
• Company to host an ampreloxetine focused virtual Key Opinion Leader (KOL) event for investors on December 8, 2025
• TRELEGY year-to-date sales on track to achieve $50 million milestone in 2025 ²
• Strong balance sheet with $333 million in cash and no debt

DUBLIN, Nov. 10, 2025 /PRNewswire/ — Theravance Biopharma, Inc. (“Theravance Biopharma” or the “Company”) (NASDAQ: TBPH) today reported financial and operational results for the third quarter of 2025.

“Theravance delivered strong results in the third quarter, highlighted by record YUPELRI net sales and the achievement of non-GAAP breakeven, underscoring our commitment to financial and operational discipline,” said Rick E Winningham, Chief Executive Officer of Theravance Biopharma. “In parallel, we continue to advance ampreloxetine toward topline results from the pivotal Phase 3 CYPRESS study in the first quarter of 2026. Backed by a strong balance sheet, durable YUPELRI cash flow, and multiple high-value milestones ahead, we approach this important catalyst from a position of strength—ready to deliver results that could transform the standard of care for multiple system atrophy patients and drive lasting value for patients and shareholders.” 

Operational Highlights:

YUPELRI ^® (revefenacin) inhalation solution, the first and only once-daily, nebulized LAMA (long-acting muscarinic antagonist) bronchodilator approved in the U.S. for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD):

• Achieved all-time high U.S. net sales of $71.4 million in Q3 2025, increasing 15% year-over-year (YoY) (Q3 2025 vs Q3 2024)¹ driven by customer demand growth of 6% YoY (Q3 2025 vs Q3 2024)³ and improved net pricing due to favorable channel mix.
• Approximately $54 million required in Q4 2025 to trigger $25 million milestone for the achievement of $250 million of net sales in 2025.⁴
• Increased doses pulled through the hospital channel by 29% YoY (Q3 2025 vs Q3 2024), reflecting another quarter of strong momentum.⁵
• Presented two oral presentations at the 2025 CHEST Annual Meeting that further support YUPELRI as an effective maintenance treatment for patients with COPD.

Ampreloxetine, an investigational, once-daily, selective norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA):

• Completed enrollment in the pivotal Phase 3 CYPRESS trial in August 2025; the open-label portion of the study has now completed, with topline results expected in Q1 2026.
• The Company continues to prepare for an expedited NDA submission and, if data are supportive, is planning to request priority FDA review.
• Theravance to host a virtual KOL event for investors on December 8, 2025, at 10:30 AM ET, featuring Dr. Horacio Kaufmann, M.D.; F. B. Axelrod Professor of Neurology and Professor of Medicine at NYU Grossman School of Medicine. The event will discuss the significant unmet need in patients with nOH due to MSA, ampreloxetine’s potential as a precision medicine approach in these patients, and if data are supportive, the significant commercial opportunity.
• A manuscript titled “Establishing Minimally Clinically Important Differences for the Orthostatic Hypotension Questionnaire (OHQ)” by Kaufmann H, et al. has been published in Clinical Autonomic Research.
• Presented one platform presentation and three poster presentations at the International Symposium on The Autonomic Nervous System. The presentations highlighted the results from the previous REDWOOD trial, where we observed a durable symptomatic nOH benefit with improvement in activities of daily living in the pre-specified subgroup analysis in patients with MSA treated with ampreloxetine.⁶ Additional data was presented on the rigorous methodologies we developed based on previous trials experience to support enrollment and patient retention in the ongoing Phase 3 CYPRESS study.

TRELEGY 

GSK reported third quarter 2025 global net sales of approximately $1.0 billion (up 24% vs. the third quarter of 2024) and year-to-date net sales of approximately $2.9 billion (up 13% vs. 2024 year-to-date):

• On track to exceed full year (FY) 2025 global net sales of ~$3.4 billion required to trigger $50 million milestone from Royalty Pharma.
  • Approximately $471 million of global net sales required in Q4 2025 to trigger the $50 million milestone.
• FY 2026 global net sales of ~$3.5 billion required to trigger an additional $100M milestone from Royalty Pharma.

Disease State Awareness

• Launched a new disease education campaign (www.nOHuncovered.com) for healthcare professionals (HCPs) to raise awareness and deepen scientific understanding of the pathophysiology underlying neurogenic orthostatic hypotension (nOH) associated with Multiple System Atrophy (MSA) in October 2025.

Third Quarter Financial Results

• Revenue: Total revenue for the third quarter of 2025 was $20.0 million, consisting entirely of Viatris collaboration revenue. Viatris collaboration revenue increased by $3.1 million, or 19%, in the third quarter compared to the same period in 2024. The Viatris collaboration revenue represents amounts receivable from Viatris and comprises the Company’s 35% share of net sales of YUPELRI, as well as its proportionate amount of the total shared commercial costs incurred by the two companies. The non-shared YUPELRI costs incurred by Theravance Biopharma are recorded within operating expenses. While Viatris records the total net sales of YUPELRI within its financial statements, Theravance Biopharma’s implied 35% share of net sales of YUPELRI for the third quarter of 2025 was $25.0 million which represented a 15% increase compared to the same period in 2024.
• Research and Development (R&D) Expenses: R&D expenses for the third quarter of 2025 were $8.1 million, compared to $9.3 million in the same period in 2024. Third quarter R&D expenses included total non-cash share-based compensation of $1.1 million.
• Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the third quarter of 2025 were $18.3 million, compared to $16.9 million in the same period in 2024. Third quarter SG&A expenses included total non-cash share-based compensation of $3.5 million.
• Share-Based Compensation: Share-based compensation expenses for the third quarter of 2025 were $4.6 million, compared to $5.0 million in the same period in 2024. Share-based compensation expenses consisted of $1.1 million for R&D and $3.5 million for SG&A in the third quarter of 2025, compared to $1.1 million and $3.9 million, respectively, in the same period in 2024.
• Income Taxes: Income tax benefit for the third quarter of 2025 was $6.5 million, compared to a $2.6 million income tax expense in the same period in 2024. The benefit reflects a favorable true-up related to taxes from the $225.0 million TRELEGY royalty sale in Q2 2025.
• Net Income: Net income was $3.6 million in the third quarter of 2025 compared to a net loss of $12.7 million in the same period in 2024. The net income benefited from the income tax benefit as noted above. Excluding the $6.5 million income tax benefit, third quarter net loss would have been $2.9 million.
• Non-GAAP Net Income from Operations⁷: Non-GAAP net income from operations was $2.3 million in the third quarter of 2025 compared to a non-GAAP net loss from operations of $2.9 million in the same period in 2024. See the section titled “Non-GAAP Financial Measures” for more information.
• Cash Position: Cash, cash equivalents and marketable securities totaled $332.7 million as of September 30, 2025.

2025 Financial Guidance 

• Operating Expenses ( excluding share-based compensation) : The Company continues to expect full year 2025 R&D expenses of $32 million to $38 million and SG&A expenses of $50 million to $60 million, in each case excluding share-based compensation.
• Share-Based Compensation: The Company continues to expect full-year share-based compensation expenses of $18 million to $20 million.
• Non-GAAP Net Income from Operations⁷: Achieved breakeven non-GAAP net income in Q3 2025; non-GAAP margin expected to remain at similar breakeven levels in Q4 2025, excluding one-time items, reflecting sustained operating discipline.

Strategic Review Committee

• Theravance Biopharma announced on November 12, 2024, that the Board of Directors had formed a Strategic Review Committee (the “Committee”), composed entirely of independent directors to assess all strategic alternatives available to the Company.
• The Company remains focused on disciplined capital allocation and returning excess cash to shareholders. The Committee will continue to evaluate a range of alternatives to further enhance shareholder value, though there can be no assurance that additional transactions will occur.

Conference Call and Live Webcast Today at 5:00 pm EST

Theravance Biopharma will hold a conference call and live webcast accompanied by slides today at 5:00 pm EST / 2:00 pm PST / 10:00 pm GMT. To participate in the live call by telephone, please pre-register here. Those interested in the live audio webcast of the conference call may access it by clicking here or visiting the Events and Presentations page under the Investors Section on Theravance Biopharma’s website.

A replay of the webcast will be available on Theravance Biopharma’s website for 30 days through December 10, 2025.

About Ampreloxetine 

Ampreloxetine, an investigational, once-daily, selective norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). The unique benefits of ampreloxetine treatment reported in MSA patients from Study 0170 included an increase in norepinephrine levels, a favorable impact on blood pressure, clinically meaningful and durable symptom improvement, and no signal for worsening of supine hypertension. In the U.S., the Company has been granted an Orphan Drug Designation for ampreloxetine for the treatment of symptomatic nOH in patients with MSA and, if results from the ongoing Phase 3 CYPRESS study are supportive, plans to file an NDA for full approval in this indication.

About CYPRESS (Study 0197), a Phase 3 Study

Study 0197 (NCT05696717) has completed enrollment. This is a registrational Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment; the primary endpoint of the study is change in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score. The Study includes four periods: screening, open label (12-week period, participants will receive a single daily 10 mg dose of ampreloxetine), randomized withdrawal (eight-week period, double-blind, placebo-controlled, participants will receive a single daily 10 mg dose of placebo or ampreloxetine), and a long-term treatment extension. Secondary outcome measures include change from baseline in Orthostatic Hypotension Daily Activity Scale (OHDAS) item 1 (activities that require standing for a short time) and item 3 (activities that require walking for a short time).

About Multiple System Atrophy (MSA) and Symptomatic Neurogenic Orthostatic Hypotension (nOH) 

MSA is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary. One of the most frequent autonomic symptoms associated with MSA is a sudden drop in blood pressure upon standing (nOH).⁸ There are approximately 50,000 MSA patients in the US⁹ and 70-90% of MSA patients experience nOH symptoms.¹⁰ Despite available therapies, many MSA patients remain symptomatic with nOH.¹¹

Neurogenic orthostatic hypotension (nOH) is a rare disorder defined as a fall in systolic blood pressure of ⩾20 mm Hg or diastolic blood pressure of ⩾10 mm Hg, within 3 minutes of standing. Severely affected patients are unable to stand for more than a few seconds because of their decrease in blood pressure, leading to cerebral hypoperfusion and syncope. A debilitating condition, nOH results in a range of symptoms including dizziness, lightheadedness, fainting, fatigue, blurry vision, weakness, trouble concentrating, and head and neck pain.

About Theravance Biopharma 

Theravance Biopharma, Inc.’s focus is to deliver Medicines that Make a Difference^® in people’s lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI^® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value.

For more information, please visit www.theravance.com.

THERAVANCE BIOPHARMA^®, THERAVANCE^® and the Cross/Star logo are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries).

YUPELRI^® is a registered trademark of Viatris Specialty LLC. Trademarks, trade names or service marks of other companies appearing on this press release are the property of their respective owners.

Forward-Looking Statements

This press release will contain certain “forward-looking” statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma, Inc. (the “Company”) intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the Company’s expectations regarding its future profitability, expenses and uses of cash, the Company’s goals, designs, strategies, plans and objectives, future growth of YUPELRI sales, future milestone or royalty payments, the ability to provide value to shareholders, the Company’s regulatory strategies and timing of clinical studies, the safety, efficacy or differentiation of our investigational therapy, commercial potential and market opportunity of our investigational therapy, the status of patent infringement litigation initiated by the Company and its partner against certain generic companies in federal district courts, and expectations around the use of OHSA scores as endpoints for clinical trials. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of this press release and the conference call and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: factors that could increase the Company’s cash requirements or expenses beyond its expectations and any factors that could adversely affect its profitability, whether the milestone thresholds can be achieved, delays or difficulties in commencing, enrolling or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the Company’s product candidates or product are unsafe, ineffective or not differentiated, risks of decisions from regulatory authorities that are unfavorable to the Company, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop, manufacture and commercialize products, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure, the ability of the Company to protect and to enforce its intellectual property rights, volatility and fluctuations in the trading price and volume of the Company’s shares, and general economic and market conditions. Other risks affecting the Company are in the Company’s Form 10-Q filed with the SEC on August 13, 2025, and other periodic reports filed with the SEC. In addition to the risks described above and in Theravance Biopharma’s filings with the SEC, other unknown or unpredictable factors also could affect Theravance Biopharma’s results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law.

Non-GAAP Financial Measures

Theravance Biopharma provides a non-GAAP profitability target and a non-GAAP metric in this press release. Theravance Biopharma believes that the non-GAAP profitability target and non-GAAP net income (loss) provide meaningful information to assist investors in assessing prospects for future performance and actual performance as they provide better metrics for analyzing the performance of its business by excluding items that may not be indicative of core operating results and the Company’s cash position. Because non-GAAP financial targets and metrics, such as non-GAAP profitability and non-GAAP net income (loss), are not standardized, it may not be possible to compare these measures with other companies’ non-GAAP targets or measures having the same or a similar name. Thus, Theravance Biopharma’s non-GAAP measures should be considered in addition to, not as a substitute for, or in isolation from, the Company’s actual GAAP results and other targets.

Please see the appendix attached to this press release for a reconciliation of non-GAAP net income (loss) to its corresponding measure, net income (loss). A reconciliation of non-GAAP net income (loss) to its corresponding GAAP measure is not available on a forward-looking basis without unreasonable effort due to the uncertainty regarding, and the potential variability of, expenses and other factors in the future.

Contact:
[email protected]
650-808-4045

SOURCE Theravance Biopharma, Inc.

The Dublin, Ohio-based chain said during a conference call with investors Friday that it planned to begin closing restaurants in the fourth quarter of this year. The company said it expected a “mid-single-digit percentage” of its U.S. stores to be affected, but it didn’t give any more details.

Wendy’s ended the third quarter with 6,011 U.S. restaurants. If 5% of those locations were impacted, it would mean 300 store closures.

The new round of closures comes on top of the closure of 240 U.S. Wendy’s locations in 2024. At the time, Wendy’s said that many of the 55-year-old chain’s restaurants are simply out of date.

Ken Cook, Wendy’s interim CEO, said Friday the company believes closing locations that are underperforming – whether it’s from a financial or customer service perspective – will help improve traffic and profitability at its remaining U.S. restaurants.

Cook became Wendy’s CEO in July after the company’s previous CEO, Kirk Tanner, left to become the president and CEO of Hershey Co.

“When we look at the system today, we have some restaurants that do not elevate the brand and are a drag from a franchisee financial performance perspective. The goal is to address and fix those restaurants,” Cook said during a conference call with investors.

Cook said in some cases, Wendy’s will make improvements to struggling stores, including adding technology or equipment. In other cases, it will transfer ownership to a different operator or close the restaurant altogether.

U.S. fast food chains have been struggling to attract lower-income U.S. consumers in the past few years as inflation has raised prices. In the July-September period, Wendy’s said its U.S. same-store sales, or sales at locations open at least a year, fell 5% compared to the same period last year.

Cook said $5 and $8 meal deals — which have been matched by McDonald’s — have helped bring some traffic back to its U.S. stores. But Wendy’s isn’t doing a good job of bringing in new customers, Cook said, so the company plans to shift its marketing to emphasize its value and the freshness of its ingredients.

Wendy’s shares dropped 7% Friday. On Monday, they were down 6% in afternoon trading.

In his annual shareholder letter—the last one he will pen as CEO before Berkshire vice chair Greg Abel takes over on Jan. 1—Buffett suggested chief executives are driven by greed and selfishness to drive up their own pay after seeing competitors ratchet up their own remunerations.

“What often bothers very wealthy CEOs—they are human, after all—is that other CEOs are getting even richer,” he said. “Envy and greed walk hand in hand. And what consultant ever recommended a serious cut in CEO compensation or board payments?”

Buffett’s remarks come on the heels of Tesla investors approving CEO Elon Musk’s record-breaking $1 trillion pay package on Thursday. The compensation package, contingent on the EV company reaching an $8.5 trillion market capitalization, would make the already-world’s-richest-man into the first trillionaire. Musk’s net worth is currently about $449 billion.

The next day, EV competitor Rivian announced a $4.6 billion compensation package for CEO RJ Scaringe over the next decade, modeled after Musk’s plan. The package, which would double Scaringe’s base salary of $2 billion, is also dependent on the automaker reaching certain operating income and cash flow targets over the next seven years.

Tesla and Rivian did not immediately respond to Fortune’s requests for comment.

Buffett, reflecting on 60 years of leading his multi-industry conglomerate, said in his letter that companies’ disclosures of CEO pay was in part an effort to make executives at least a little self-conscious about the amount of money they were earning. However, what was intended as a gesture to humble instead became a contest of superiority.

“During my lifetime, reformers sought to embarrass CEOs by requiring the disclosure of the compensation of the boss compared to what was being paid to the average employee,” Buffett said. “Proxy statements promptly ballooned to 100-plus pages compared to 20 or less earlier. But the good intentions didn’t work; instead they backfired.” 

“Based on the majority of my observations—the CEO of company ‘A’ looked at his competitor at company ‘B’ and subtly conveyed to his board that he should be worth more. Of course, he also boosted the pay of directors and was careful who he placed on the compensation committee,” he added. “The new rules produced envy, not moderation.”

Indeed, compensation packages have swelled extravagantly, climbing 34.7% among the U.S.’s 100 largest low-wage employers from 2019 to 2024, according to an August report from the Institute for Policy Studies. The CEO-to-worker pay ratio similarly ballooned, growing from 560:1 in 2019 to 632:1 last year. Inordinate pay packages have helped make the country’s wealthiest billionaires $698 billion richer this year, per an Oxfam report published this month. Buffett, in contrast, has an annual salary of $100,000 (though his net worth sits at around $150 billion thanks to his investments, making him the 11th richest person on earth).

Other financial giants have spoken out against exorbitant pay packages, Musk’s in particular. Norges Investment Management, the entity behind Norway’s $2 trillion sovereign wealth fund and a 1.14% stakeholder in Tesla, voted against Musk’s compensation plan.

“While we appreciate the significant value created under Mr. Musk’s visionary role,” the group said in a statement last week, “we are concerned about the total size of the award, dilution, and lack of mitigation of key person risk—consistent with our views on executive compensation.”

Following the March 2025 decision by the FDA to expand the indication of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to include adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have received an androgen receptor pathway inhibitor (ARPI) for whom a delay of taxane-based chemotherapy is appropriate, key factors such as the nature of disease progression and patient preferences and treatment goals must be carefully weighed to properly identify ideal candidates for this approach, according to Daniel J. George, MD.¹

Radioligand Therapy vs Chemotherapy in mCRPC

• In March 2025, the FDA expanded the indication of lutetium Lu 177 vipivotide tetraxetan to include adult patients with PSMA-positive mCRPC who have received an ARPI and for whom a delay of taxane-based chemotherapy is appropriate.

• Factors to consider when selecting between lutetium Lu 177 vipivotide tetraxetan and chemotherapy in this setting include the nature of disease progression, patient- and disease-related factors, and patient preference.

• Ongoing studies could help define a role for radioligand therapy in earlier prostate cancer settings.

The regulatory decision was based on data from the phase 3 PSMAfore trial (NCT04689828), which showed that patients who received the radioligand therapy achieved a significant radiographic progression-free survival compared with those who transitioned to another ARPI (HR, 0.41; 95% CI, 0.29-0.56; P < .0001). The expanded indication followed the initial March 2022 FDA approval of the agent for the treatment of adult patients with PSMA-positive mCRPC who previously received an ARPI and taxane-based chemotherapy.²

In an interview with OncLive®, George, the Eleanor Easley Distinguished Professor in the School of Medicine, Medicine, Medical Oncology, a professor of Medicine, Medicine, Medical Oncology; and a professor in urology at Duke Health in Durham, North Carolina, discussed which patients he considers for treatment with lutetium Lu 177 vipivotide tetraxetan, the future of radioligand therapy in prostate cancer, and other novel treatment approaches being investigated for patients who experience disease progression on an ARPI-based regimen.

OncLive: What is your approach for treating patients with mCRPC who experience disease progression following an ARPI-based regimen?

George: When patients have metastatic hormone-sensitive prostate cancer [(mHSPC) and are receiving] an ARPI, the prognosis can be quite good in some cases, particularly in those with good prostate-specific antigen [PSA] responses. As the disease progresses into castration-resistant metastatic disease on an ARPI, the clock is ticking.

These are patients who need to be aware, even if they feel well and asymptomatic, that their life expectancy is in that 2-to-3-year range, and it’s not indefinite. The changes are going to come quicker; the need to take on potentially more adverse effects with cytotoxic therapy is going to be greater, and [we need] to recognize that the expectations of therapy are going to be more modest in this setting. With all that said, it’s a spectrum. We have patients who have slow PSA rising and minimal metastatic disease burden on ARPI, for whom we’re going to be comfortable doing a clinical trial of an investigational, unproven agent. We’re going to be comfortable using sipuleucel-T [Provenge] and other types of less immediately cytotoxic therapies.

[Many] patients will have more rapidly progressive disease, higher volume disease, and risk of complications and symptoms. For those patients, using cytotoxic therapy, whether that’s taxane-based therapy or a radioligand therapy, [such as] lutetium Lu 177 vipivotide tetraxetan, is the first major treatment decision.

What are some of the factors you consider when deciding to give chemotherapy or deferring it in favor of radioligand therapy to a patient with mCRPC who is eligible for both treatments?

When I’m addressing a patient at that critical juncture of post-ARPI with disease progression, I’m looking at a couple of things. How is that disease progression? Is it clinical? Is it radiographic? Is it PSA only? Is it a combination of all 3? I’m looking at their tumor volume as well, and at whether the patient is a chemotherapy candidate.

In the real world, a lot of ou r patients are just not good chemotherapy candidates. [Even] if they are, it’s going to come at a physical cost. They [are often] frail and [have] other [comorbidities] that are going to clinically worsen from that chemotherapy. These are the factors that I [use to determine] whether they’re good up-front chemotherapy candidates. If they are willing, starting chemotherapy is a good choice because we know that lutetium Lu 177 vipivotide tetraxetan has an [overall] survival [OS] benefit post-chemotherapy.

We also know that [lutetium Lu 177 vipivotide tetraxetan] has a significant benefit prechemotherapy, and for many of our patients who are not chemotherapy candidates. I use chemotherapy fitness as my first judge, and then it’s patient preference. At the end of the day, they get a voice and this a shared decision. A lot of patients want to put chemotherapy off until they really need to do it, and I’m perfectly comfortable with that. Starting with lutetium Lu 177 vipivotide tetraxetan in the majority of patients is absolutely a reasonable course.

What is your approach to PSMA testing when you are considering using lutetium Lu 177 vipivotide tetraxetan?

[To me, when a patient] has emerging castrate resistance in their disease, that’s the best time to get a PSMA-PET scan. First, it’s our best staging. It’s our most sensitive test for assessing the full extent of the disease, and it gives me peace of mind that there isn’t visceral disease hiding in there. If it is lymph node–only disease, I can feel confident there isn’t [disease] in the bone. Importantly, if there’s oligometastatic disease, if these patients have 1 or 2 areas that are growing but really the rest of the disease is still ARPI responsive, I’ll consider some of these are patients for tumor-directed radiotherapies.

It’s also a theranostic for lutetium Lu 177 vipivotide tetraxetan and I use it as such. It’s important also to be able to gauge at this point in time how ubiquitous and intense that PSMA uptake is. I’m also talking with my nuclear medicine physicians about the scan and their interpretation.

Where do you see the story of radioligand therapy going next within the prostate cancer treatment paradigm?

Lutetium Lu 177 vipivotide tetraxetan has shown us is that there is a role for this therapy throughout the disease continuum, from hormone-sensitive disease all the way through chemotherapy-refractory castration-resistant disease. Not unlike how ARPIs were developed, the goalposts have changed as we move into these other disease spaces.

I’m less worried about being able to see the OS end points as we move earlier and earlier [into new disease settings], because there are so many other things that affect the outcomes in these patients. I’m more interested in the ability to get to minimal residual disease [MRD]. If we think about what our goals are for patients with early mHSPC, historically we’ve [designed] the registrational trials to look at rPFS and OS, but if you talk about our patients, those aren’t necessarily their goals. They want to get to MRD and to get off therapy.

In the future, if radioligand therapies are part of the mix of treatments, whether they be up-front combinations or induction followed by consolidation or maintenance therapy, they may allow us to get patients off treatment—maybe not all patients, but some patients in the metastatic, hormone-sensitive setting. That’s going to be an important aspect of this.

Our goal as patient advocates is ultimately to come up with a combination or sequence of therapies that get us to MRD in the greatest number of patients and ultimately get patients off treatment. If that’s a cure, that’s wonderful, but even a break from therapy for these patients is welcome in order to restore some of their functionality and overall health.

Are there any novel agents being developed for patients with mCRPC that are of particular interest to you?

It’s probably one of the most exciting times in prostate cancer drug development right now. We have more mechanisms to target now than ever before, and what started out as just basically the AR pathway has now expanded to PSMA-targeted approaches—not just radioligands, but potentially antibody-drug conjugates and bispecific antibodies.

Beyond PSMA, we’re seeing evidence for [targeting] KLK2 and STEAP2 [alterations]. We’re getting more targets in prostate cancer, and we’re getting mechanisms to start targeting. Other targets that are drivers of more aggressive forms of prostate cancer, and more androgen-independent forms of prostate cancer are coming into clinic. This is an incredibly important aspect, because before we were limited to what we could target in prostate cancer. We’d get these next-generation sequences and our big list of mutations, and things would be non-actionable.

You’re going to see now more and more actionable targets in that profiling is going to become more and more critical in how we’re treat these patients. That’s going to make the testing and diagnostics all the more important. And I hope you know that today, we can already justify doing that on a systematic level for everybody with advanced prostate cancer, knowing that these therapies are coming.

References

1. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed November 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication
2. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. March 23, 2022. Accessed November 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer?utm_medium=email&utm_source=govdelivery

The S&P 500 climbed 1.3% to claw back three-quarters of its drop from last week, which was its first weekly loss in four. The Dow Jones Industrial Average was up 245 points, or 0.5%, as of 1:15 p.m. Eastern time, and the Nasdaq composite was 2.1% higher.

Nvidia was by far the strongest force lifting the market and rallied 4.8%. It’s a bounceback after Nvidia and other winners in the frenzy around artificial-intelligence technology were at the center of last week’s drop. Critics say their stock prices shot too high and too fast in the mania around AI, drawing comparisons to the 2000 dot-com bubble that ultimately burst.

Taiwan Semiconductor Manufacturing Co., which makes chips for Nvidia and other companies, saw its stock that trades in United States rise 3.1% after reporting that its revenue climbed nearly 17% in October from a year earlier. While such growth is strong compared with other companies, it’s a slowdown from TSMC’s earlier performance.

Another AI darling, Palantir Technologies, jumped 8.9% for the biggest gain in the S&P 500. That helped it recover some of its loss since it delivered a profit report last week that topped analysts’ expectations.

Losses for health insurers helped keep the market’s gains in check, though. They fell as uncertainty remains about whether Washington will extend expiring health care tax credits, a sticking point on Capitol Hill that’s created the longest-ever shutdown for the U.S. government.

That’s even as the Senate took the first steps on Sunday to end the shutdown.

President Donald Trump suggested in a social media post over the weekend that cash being sent to “money sucking” insurance companies should instead go directly to people so they can buy their own health insurance.

Humana fell 3.3%, Elevance Health sank 3.8% and Centene dropped 7.6%.

The effects of the government’s shutdown have become more apparent following the cancellations of thousands of flights over the weekend. Towers are facing shortages as some air traffic controllers — unpaid for weeks — have stopped showing up for work.

Besides the pain at airports, the U.S. government’s shutdown has also delayed important reports on the economy. A resumption could upset financial markets if the released logjam shows data that dashes traders’ expectations for coming cuts to interest rates.

The wide expectation is for the Federal Reserve to continue cutting its main interest rate in hopes of shoring up what has been a slowing job market. Wall Street loves lower interest rates because they can give the economy a boost while also pushing prices for investments upward.

But the Fed has said it may have to halt its cuts if inflation worsens because lower interest rates can give inflation more fuel.

Without updates from the U.S. government on jobs and the economy, traders have instead been trawling profit reports from companies for clues about how things are going.

Tyson Foods climbed 1.6% after the seller of chicken and other proteins reported a stronger profit for the latest quarter than analysts expected. It benefited from increases in prices for its pork and beef of 11% to 17%.

Roughly four out of every five companies in the S&P 500 that have reported their results for the summer have also topped analysts’ profit expectations so far, according to FactSet. Companies usually beat analysts’ estimates each quarter, but the pressure was high this time around because they needed to justify the big moves upward for their stock prices since April.

Delivering bigger profits is one of the easier ways companies can quiet criticism that their stock prices have become too expensive.

Companies have also been giving generally strong forecasts for upcoming results, according to Bank of America strategist Savita Subramanian. That has analysts’ expectations for earnings in 2026 nearly all the way back to where they were before Trump shocked financial markets with his “Liberation Day” announcement of worldwide tariffs in April.

In stock markets abroad, indexes rallied across much of Europe and Asia.

South Korea’s Kospi jumped 3% for one of the bigger gains. Chip company SK Hynix, which is cooperating with Nvidia on artificial intelligence, leaped 4.5%. Its bigger rival, Samsung Electronics, climbed 2.8%.

In the bond market, the yield on the 10-year Treasury edged down to 4.10% from 4.11% late Friday.

Wendy’s plans to close hundreds U.S. restaurants over the next few months in an effort to boost its profit.

The Dublin, Ohio-based chain said during a conference call with investors Friday that it planned to begin closing restaurants in the fourth quarter of this year. The company said it expected a “mid-single-digit percentage” of its U.S. stores to be affected, but it didn’t give any more details.

Wendy’s ended the third quarter with 6,011 U.S. restaurants. If 5% of those locations were impacted, it would mean 300 store closures.

The new round of closures comes on top of the closure of 240 U.S. Wendy’s locations in 2024. At the time, Wendy’s said that many of the 55-year-old chain’s restaurants are simply out of date.

Ken Cook, Wendy’s interim CEO, said Friday the company believes closing locations that are underperforming – whether it’s from a financial or customer service perspective – will help improve traffic and profitability at its remaining U.S. restaurants.

Cook became Wendy’s CEO in July after the company’s previous CEO, Kirk Tanner, left to become the president and CEO of Hershey Co.

“When we look at the system today, we have some restaurants that do not elevate the brand and are a drag from a franchisee financial performance perspective. The goal is to address and fix those restaurants,” Cook said during a conference call with investors.

Cook said in some cases, Wendy’s will make improvements to struggling stores, including adding technology or equipment. In other cases, it will transfer ownership to a different operator or close the restaurant altogether.

U.S. fast food chains have been struggling to attract lower-income U.S. consumers in the past few years as inflation has raised prices. In the July-September period, Wendy’s said its U.S. same-store sales, or sales at locations open at least a year, fell 5% compared to the same period last year.

Cook said $5 and $8 meal deals — which have been matched by McDonald’s — have helped bring some traffic back to its U.S. stores. But Wendy’s isn’t doing a good job of bringing in new customers, Cook said, so the company plans to shift its marketing to emphasize its value and the freshness of its ingredients.

Wendy’s shares dropped 7% Friday. On Monday, they were down 6% in afternoon trading.

 

Some of the largest chemical companies in the world—Arkema, BASF, Cargill, Dow, and LG Chemical among them—have attempted to make acrylic acid via a biobased route. It stands to reason that they would. The product is the key raw material for making the superabsorbent polymers found in diapers and incontinence products, which have a reputation for generating a lot of waste. Acrylic acid derivatives are also ubiquitous in acrylic paints and adhesives. To make it from renewable raw materials rather than fossil fuels would be a big win.

“The market has desired a biobased acrylic for quite some time, 20-some-odd years at this point, and no one’s ever made the economics work,” says Christopher P. Nicholas, chief technology officer and cofounder of Låkril Technologies.

Nicholas thinks Låkril has the catalyst that will allow the firm to succeed where others have failed.

The conventional process for making acrylic acid is the oxidation of propylene into acrolein, followed by another oxidation into acrylic acid. This petrochemical pathway is responsible for nearly all the 7 million metric tons (t) of acrylic acid produced annually around the world.

Companies have attempted two main routes to a biobased alternative, both involving dehydration of a monomer made via sugar fermentation. One—tried by firms such as BASF, Cargill, and Dow—starts with 3-hydroxypropionic acid (3-HP). The other is based on lactic acid, a pathway that Cargill is investigating with technology licensed from the diaper producer Procter & Gamble.

The lactic acid route has its appeal. 3-HP is not made in significant quantities, whereas lactic acid has been commercially produced via fermentation since the 1880s, Nicholas points out. Today, about 2 million t of it is made annually by companies like Cargill and Corbion via fermentation of sugars from corn or other local crops. The lactic is then used to produce derivatives such as the biobased polymer polylactic acid.

The chemistry of lactic acid is challenging, however. “The two molecules—the feedstock lactic acid and the product acrylic acid—are probably two of the most reactive molecules I’ve had to work with over the course of my career,” Nicholas says. “Both of them love to polymerize, and it’s why they’re essentially good monomers, but it’s also quite a pain to work with them in the lab.”

In addition, being an α-hydroxy acid, lactic acid is more difficult to dehydrate than 3-HP, which is a β-hydroxy acid. This obstacle is a reason that, despite the commercial availability of lactic acid, many firms have pursued a 3-HP route.

Låkril’s catalyst gives the lactic acid route the advantage by achieving dehydration better than any previous effort had, according to Nicholas. The catalyst was discovered in 2020 at the University of Minnesota Twin Cities lab of chemical engineer Paul J. Dauenhauer, a Låkril cofounder. Dauenhauer had been working on improvements to zeolite catalysts for the transformation of lactates into acrylates. He found that bifunctional zeolite catalysts with engineered bases could control the dehydration of α-hydroxy acids with high efficiency.

Nicholas says the catalyst produces acrylic acid at a yield of 90%. Previous efforts at dehydration of lactic acid achieved yields of only 80–85%.

“The largest contributor to the cash cost of production of bio-acrylic acid is the lactic acid,” Nicholas says. “You can’t afford to throw any of the feedstock away as off-spec product. So the biggest thing that you need is high selectivity.”

Nicholas contends that its more efficient catalyst makes Låkril’s process competitive with even the petrochemical route. A plant using Låkril’s catalyst to produce 40,000 t of acrylic acid per year would have cost parity with a propylene-based plant, he says.

With their promising catalyst in hand, Dauenhauer and Nicholas formed Låkril in 2021. Later that year, the start-up won the Consider Corn Challenge, a contest sponsored by the National Corn Growers Association. In 2022, the firm raised money in a preseed funding round led by Iowa Corn. Låkril has also been awarded over $2 million in federally funded research grants from the US Departments of Energy and Agriculture, as well as from the US National Science Foundation.

Earlier this year, Låkril closed a $3.2 million seed funding round, bringing its total funding to approximately $7 million. With that round came a well-connected backer: GC Ventures America, the venture capital arm of the Thai petrochemical giant PTT Global Chemical. PTT owns Allnex, a coating resin maker that uses acrylic resins. PTT also is a 50% shareholder in NatureWorks, a polylactic acid joint venture with Cargill. Låkril aims to pursue a series A financing round in 2026.

Later this year, the company will start up a continuously operating pilot plant in Chicago that will have the capacity to produce 4 kg of acrylic acid per day. In addition to fine-tuning Låkril’s process for scale-up, the plant will provide sample quantities to acrylic acid users. To assist the company as it begins commercialization, it has hired Justin Brown as CEO. Brown is an energy industry veteran, with experience at Honeywell UOP.

Låkril’s long-term vision is to license its technology and provide the catalyst to a third party that would build the first plant, perhaps a demonstration plant that produces 1–10 t per day. If Låkril reaches that stage, it will have succeeded where for decades many larger firms have fallen short.