On May 14, 2025 IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines, reported financial results and business highlights for the first quarter of 2025 (Press release, IO Biotech, MAY 14, 2025, View Source [SID1234653062]). The company continues to advance its pipeline, presenting new data further defining the mechanism of action for its T-Win therapeutic cancer vaccines, and reaffirming its expectation that the Phase 3 pivotal trial will readout in the third quarter of 2025.

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"IO Biotech continues to make meaningful progress developing novel cancer therapies that are designed to address significant unmet needs in melanoma and other hard-to-treat cancers, and we are thrilled to be recognized for our work by Fast Company as one of the most innovative companies in the world," said Mai-Britt Zocca, PhD, President and CEO of IO Biotech. "This year, we remain focused on delivering our Phase 3 data, preparing a Biologics License Application (BLA) and planning for commercialization of Cylembio (imsapepimut and etimupepimut, adjuvanted), our potentially first-in-class, immune-modulatory, off-the-shelf therapeutic cancer vaccine."

Dr. Zocca continued, "Additionally, we continue to explore potential collaborations to expand the global impact of our product candidates and our platform across multiple cancer types."

Recent Business Highlights

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The company’s pivotal Phase 3 trial (IOB-013/KN-D18) is progressing as planned with the readout of the primary endpoint of progression free survival (PFS) still expected in the third quarter of 2025. The trial is evaluating the company’s lead investigational vaccine, Cylembio (imsapepimut and etimupepimut, adjuvanted), in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of advanced melanoma. The company continues to plan to submit a BLA to the U.S. Food & Drug Administration (FDA) in 2025 for Cylembio and, subject to FDA approval, launch a potentially first-in-class therapeutic cancer vaccine for patients with advanced melanoma in the US in 2026.

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The company completed enrollment in its perioperative Phase 2 solid tumor basket trial (IOB-032/PN-E40), studying treatment with Cylembio in combination with pembrolizumab in patients with resectable squamous cell carcinoma of the head and neck (SCCHN) and melanoma in January. The company expects initial data from the perioperative trial as well as longer-term data from the company’s other ongoing Phase 2 basket trial, IOB-022/KN-D38, in patients with advanced SCCHN or non-small cell lung cancer (NSCLC) in the second half of 2025.

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On May 6, 2025, the company announced that it drew tranche A (€10.0 million) from the loan facility it entered into with the European Investment Bank (EIB) in December 2024. The company also believes that it has satisfied the conditions for the second tranche (€12.5 million) of the EIB loan facility.

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IO Biotech was named to Fast Company’s World’s Most Innovative Companies of 2025 list for its potentially game-changing approach to immune-modulatory cancer vaccines, earning its place on the coveted list as the 9th most innovative company in the world in the biotechnology category.

Upcoming Investor Conferences

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TD Cowen’s 6th Annual Oncology Innovation Summit: Insights for ASCO (Free ASCO Whitepaper) & EHA (Free EHA Whitepaper): Mai-Britt Zocca, PhD, President and CEO, Amy Sullivan, CFO, and Qasim Ahmad, MD, CMO, will participate in a fireside chat beginning at 10:30 AM ET on May 27, 2025.

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Jefferies Global Healthcare Conference: Mai-Britt Zocca, PhD, President and CEO, will give a presentation beginning at 7:35 AM ET on June 4, 2025.

The webcasts for these two upcoming conferences will be available from the Investors section of the company’s website at View Source

First Quarter 2025 Financial Results

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Net loss for the three months ended March 31, 2025, was $22.4 million, compared to $19.5 million for the three months ended March 31, 2024.

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Research and development expenses were $16.4 million for the three months ended March 31, 2025, compared to $14.3 million for the three months ended March 31, 2024. The company recognized $0.6 million in research and development equity-based compensation for the three months ended March 31, 2025 and 2024, respectively.

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General and administrative expenses were $6.2 million for the three months ended March 31, 2025, compared to $5.9 million for the three months ended March 31, 2024. The company recognized $1.0 million in general and administrative equity-based compensation for the three months ended March 31, 2025 and 2024, respectively.

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Cash and cash equivalents as of March 31, 2025 were $37.1 million, compared to $60.0 million at December 31, 2024. During the three months ended March 31, 2025, the company used cash, cash equivalents and restricted cash of $22.9 million. On May 6, 2025, the company drew tranche A of the EIB loan facility of €10.0 million before payment of certain fees and transaction related expenses. The company continues to expect that it will have sufficient cash to run the company into the second quarter of 2026, assuming draw down of the first three committed tranches of the EIB loan facility.

About Cylembio

Cylembio (imsapepimut and etimupepimut, adjuvanted) is an investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine candidate designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase 1 (IDO1) positive and/or programmed death-ligand 1 (PD-L1) positive cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating Cylembio in combination with pembrolizumab as first line treatment in patients with advanced solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating Cylembio in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors. Enrollment in the three ongoing company-sponsored clinical trials is now complete.

The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck, which is supplying pembrolizumab. IO Biotech maintains global commercial rights to Cylembio.

Cylembio is a registered trademark of IO Biotech ApS, a subsidiary of IO Biotech.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About the IOB-013/KN-D18 Pivotal Phase 3 Clinical Trial

IOB-013/KN-D18 (ClinicalTrials.gov: NCT05155254) is an open label, randomized Phase 3 pivotal clinical trial evaluating Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. A total of 407 patients have been enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study is progression free survival. Top-line data readout is expected in the third quarter of 2025. Secondary endpoints include overall response rate, overall survival, durable objective response rate, complete response rate, duration of response, time to complete response, disease control rate, and incidence of adverse events and serious adverse events (safety and tolerability). Biomarkers in the blood and tumor tissue will also be assessed as exploratory endpoints. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab.

About IOB-022/KN-D38 Phase 2 Solid Tumor Basket Trial

IOB-022/KN-D38 (NCT05077709) is a non-comparative, open label trial to investigate the safety and efficacy of Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in the first-line treatment of metastatic non-small cell lung cancer (NSCLC) or metastatic squamous cell carcinoma of the head and neck (SCCHN) at sites in the United States, Spain, and the United Kingdom. IO Biotech is sponsoring the Phase 2 trial and Merck is supplying pembrolizumab.

About IOB-032/PN-E40 Phase 2 Solid Tumor Basket Trial

IOB-032/PN-E40 (NCT05280314) is a multicenter Phase 2 basket trial investigating Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) as neo-adjuvant/adjuvant treatment of patients with solid tumors at sites in Australia, the United States, France, Germany, Spain, and Denmark. The study completed enrollment in all cohorts: 18 patients with melanoma in cohort A and 16 patients with SCCHN in cohort B, both as single arm cohorts receiving combination of Cylembio with pembrolizumab. In cohort C, 61 melanoma patients were randomized 1:1 to either the combination of Cylembio with pembrolizumab or pembrolizumab alone. In the neo-adjuvant period, for all cohorts, treatment is every 3 weeks (Q3W) for 3 cycles (melanoma) or 2-3 cycles (SCCHN). Patients entering the study will be scheduled for surgery and begin neoadjuvant treatment 4-9 weeks prior. Surgery will be followed by adjuvant treatment with the same regimen for 15 cycles. Cohort C patients with poor pathological response to pembrolizumab alone in the neo-adjuvant phase (>10% residual viable tumor) may cross over to combination treatment post-surgery. The primary endpoint is major pathological response at surgery (≤10% residual viable tumor; central assessment). IO Biotech is sponsoring the Phase 2 trial and Merck is supplying pembrolizumab.

On May 14, 2025 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company developing a potentially first-in-class and best-in-class WEE1 inhibitor for patients with ovarian cancer and other tumor types, reported financial results for the first quarter 2025 and highlighted recent operational progress (Press release, Zentalis Pharmaceuticals, MAY 14, 2025, View Source [SID1234653082]).

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"We continued advancement of azenosertib and made solid progress against our strategic goals in the first quarter. The initiation of DENALI Part 2 moves us into a new chapter as a late-stage development company focusing on a significant patient population in platinum-resistant ovarian cancer with limited choices." said Julie Eastland, Chief Executive Officer of Zentalis. "Our team remains focused on the enrollment and execution of DENALI. Zentalis is financially and organizationally well-positioned to continue advancing azenosertib as a potential treatment option for PROC patients."

Program Highlights

•First patient dosed in Part 2 of the Phase 2 DENALI clinical trial.
◦In April 2025, the Company announced that the first patient had been dosed in Part 2a of the Phase 2 DENALI clinical trial (NCT05128825) of azenosertib in patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC).
◦Part 2a is designed to confirm the primary dose-of-interest with a target enrollment of approximately 30 patients at each of two dose levels: 400mg QD 5:2 and 300mg QD 5:2 (intermittent daily dosing with a five days on, two days off dosing schedule).
◦The Company expects to disclose topline data from DENALI Part 2 (Part 2a and Part 2b) by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review.

•Azenosertib clinical data demonstrated clinically meaningful response rates and a consistent therapeutic profile.
◦Previously disclosed clinical data from Part 1b of the DENALI study showed clinically meaningful results in patients with Cyclin E1+ PROC. As of the January 13, 2025 data cutoff, patients who were response-evaluable (n=43) had an objective response rate (ORR) of 34.9% and a median duration of response (mDOR) of 6.3 months. The mDOR is subject to change as there were patients with ongoing responses as of the cutoff date.
◦Across multiple monotherapy studies of azenosertib with significant sample sizes, as of the December 2, 2024 data cutoff, azenosertib demonstrated meaningful antitumor activity (ORR >30% at 400mg QD 5:2) and a manageable safety profile in Cyclin E1+ PROC patients.

Upcoming Events

•Zentalis plans to participate in the following scientific and medical conference:
◦American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting – May 30 to June 3 in Chicago, IL
◦NRG Oncology Summer Meeting – July 24 to 26 in Washington, D.C.

•Zentalis plans to participate and present in the following investor events:
◦H.C. Wainwright 3rd Annual BioConnect Investor Conference – May 20 in New York, NY
◦TD Cowen’s 6th Annual Oncology Innovation Summit – May 27 Virtual
◦Jefferies Healthcare Conference – June 4 in New York, NY

First Quarter 2025 Financial Results

•Cash, Cash Equivalents and Marketable Securities Position: As of March 31, 2025, the Company had cash, cash equivalents and marketable securities of $332.5 million, which includes $12.2 million representing the March 31, 2025 fair value of Immunome common stock received by the Company from the sale of its ROR1 antibody-drug conjugate (ADC) product candidate and ADC platform to Immunome in October 2024. The Company believes that its existing cash, cash equivalents and marketable securities as of March 31, 2025 will be sufficient to fund its operating expenses and capital expenditure requirements into late 2027.

•Research and Development Expenses: Research and development expenses for the three months ended March 31, 2025 were $27.2 million, compared to $49.6 million for the three months ended March 31, 2024. The decrease of $22.4 million was primarily due to decreases of $10.7 million for clinical expenses, $4.8 million for drug manufacturing, $3.5 million for lab services and $5.1 million related to consulting and personnel expenses including non-cash stock-based compensation. These decreases were partially offset by a one-time impairment charge of $1.2 million related to the disposal of research and development equipment and an increase of $0.5 million of allocated overhead.

•General and Administrative Expenses: General and administrative expenses for the three months ended March 31, 2025 were $10.6 million, compared to $15.7 million during the three months ended March 31, 2024. This decrease of $5.1 million was primarily attributable to non-cash stock-based compensation.

•Operating Expenses: Total operating expenses were $45.6 million for the three months ended March 31, 2025, compared to $65.3 million for the three months ended March 31, 2024. Total operating expenses for the first quarter of 2025 include the non-recurring restructuring expenses of $7.8 million associated with the strategic restructuring announced in January 2025.

About Azenosertib

Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.

About DENALI Clinical Trial

DENALI is a multi-part Phase 2 clinical trial studying azenosertib in platinum-resistant ovarian cancer (PROC) patients. Part 1b enrolled patients with PROC regardless of Cyclin E1 protein expression, all treated at 400mg 5:2(intermittent daily dosing with a five days on, two days off dosing schedule). Interim results from Part 1b were presented at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting. Part 2 is ongoing and is enrolling PROC patients with Cyclin E1 protein overexpression based on Zentalis’ proprietary immunohistochemistry cutoff. Part 2 includes Part 2a, a dose confirmation portion evaluating two doses, 300mg 5:2 and 400mg 5:2, and Part 2b, a portion designed to complete enrollment at the selected dose. Part 2, in total, is designed for accelerated approval, pending study outcome and discussions with the U.S. Food and Drug Administration.

On May 14, 2025 Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine and patient care, reported a new strategic collaboration to advance Boehringer Ingelheim’s growing cancer pipeline (Press release, Tempus, MAY 14, 2025, View Source [SID1234653101]). The new, multi-year collaboration builds on foundational work the two companies have conducted in the last few years, leveraging data and AI to further advance therapeutic research and development.

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Despite significant breakthroughs in the understanding, prevention, and treatment of cancer, the disease remains a major challenge, impacting millions of lives and straining healthcare systems. Boehringer Ingelheim is committed to changing this by advancing the discovery and development of new breakthrough treatments for people living with hard-to-treat cancers. With this new collaboration, Boehringer will have access to Tempus’ de-identified database containing molecular, clinical, and imaging data and its analytical platform, Lens. The aim is to explore data derived from patient cohorts to guide biomarker development and patient stratification, develop drug combination hypotheses, support novel target discovery efforts, and educate on patients’ healthcare journey.

"By combining internal, pre-clinical experimental data, with real-world data from Tempus on its AI-powered platform, we can profoundly deepen our understanding of cancer biology and accelerate our drug discovery and development efforts," said Mark Paul Petronczki, Head of Oncology Research at Boehringer Ingelheim.

"Leveraging real-world patient data is crucial for strengthening our data foundation and harnessing advanced AI methodologies, ultimately accelerating drug development. Integrating these comprehensive datasets with our internal data and techniques not only drives innovation but also enhances the precision and efficiency of pharmaceutical research, paving the way for groundbreaking medical advancements. I am very excited to continue our collaboration with Tempus," stated Jan Nygaard Jensen, Head of Computational Innovation at Boehringer Ingelheim.

"We look forward to expanding our work with the Boehringer team and the opportunity to deploy multiple of our solutions to their growing oncology pipeline," said Ryan Fukushima, Chief Operating Officer at Tempus. "We both are firmly committed to applying the power of data and AI to this important research to bring novel treatments to patients faster."

On May 14, 2025 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, reported that new data on the company’s PK activators, mitapivat and tebapivat, will be featured in oral and poster presentations during the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA 2025) in Milan, Italy, June 12-15, 2025 (Press release, Agios Pharmaceuticals, MAY 14, 2025, View Source [SID1234653048]).

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"The clinical results and scientific insights being presented at EHA (Free EHA Whitepaper) add to the robust body of efficacy and safety data demonstrating the promise of PK activation in treating both adults and children with rare blood disorders," said Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and Head of R&D, Agios. "The presentations span serious conditions with limited or no treatment options, including sickle cell disease, thalassemia, PK deficiency, and myelodysplastic syndromes, offering meaningful results that highlight the therapeutic potential of mitapivat and tebapivat. We look forward to this important opportunity to share these new data and strengthen our collaboration with the global hematology community at EHA (Free EHA Whitepaper)."

Select presentations and publications at EHA (Free EHA Whitepaper) 2025 will include:

An oral presentation of results from the ACTIVATE-KidsT Phase 3 study of mitapivat in children aged 1 to <18 years with PK deficiency who are regularly transfused. The study showed a clinically meaningful reduction in transfusion burden with mitapivat, with a higher proportion of patients achieving the primary endpoint of transfusion reduction response compared to placebo, though the prespecified statistical criterion was not met. Safety results were consistent with the safety profile for mitapivat previously observed in adults with PK deficiency who are regularly transfused. The ACTIVATE-KidsT study, along with the positive ACTIVATE-Kids Phase 3 trial, represents the successful execution of Agios’ first pediatric clinical program.
An oral presentation of long-term data from the investigator-led ESTIMATE Phase 2 trial, an open-label study investigating mitapivat in patients with sickle cell disease. In the study, mitapivat showed sustained efficacy and tolerability over three years, including improvements in anemia, hemolysis, painful vaso-occlusive crises, and markers of kidney damage.
A poster presentation with preclinical data demonstrating that tebapivat reduced red blood cell sickling and adhesion in blood samples from sickle cell disease patients, highlighting its therapeutic potential in this patient population.
A preclinical publication examining expression patterns of PKM2, an isoform (or variant) of the PK enzyme. The study found that, compared with healthy controls, patients with myelodysplastic syndromes (MDS) have significantly reduced PKM2 expression in CD34+ hematopoietic stem cells, which may be implicated in the development of MDS. These findings further support the ongoing investigation of tebapivat in lower-risk MDS, as it activates PKM2 in addition to PKR (the PK isoform found in red blood cells).
In total, 14 presentations and publications led by Agios and external collaborators will be shared at EHA (Free EHA Whitepaper) 2025.

EHA 2025 Accepted Abstracts

Title Number Date/Time Presenter Acceptance
Thalassemia
Overall survival and morbidity among adults with thalassemia in England: A retrospective analysis using routinely collected healthcare data from 2008 to 2020 PS2183

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Khaled M. Musallam, M.D., Ph.D., Burjeel Medical City, Abu Dhabi, United Arab Emirates

Poster
Impact of non-transfusion-dependent thalassemia on adult patients’ health-related quality of life and work productivity: A multi-region real-world survey PF1192

Friday, June 13, 2025, 6:30 – 7:30 PM CEST

Khaled M. Musallam, M.D., Ph.D., Burjeel Medical City, Abu Dhabi, United Arab Emirates

Poster
ENERGIZE-T/ENERGIZE: Roxyscan assesses pyruvate kinase activator’s effect on oxidative stress sensitivity in β-thalassemia patients PS2192

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Eduard J. van Beers, M.D., Ph.D., University Medical Center of Utrecht, Netherlands Poster
Understanding health literacy among patients with thalassemia: Initial key learnings from a global patient survey by the Thalassemia Advocacy Advisory Council PB3545

N/A Maria Domenica Cappellini, M.D., University of Milan, Italy Publication
Sickle Cell Disease
Three-year safety, efficacy, and renal outcomes of mitapivat treatment in sickle cell disease: Results from a phase 2, open-label study S299

Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Geoffrey Kuppens, University Medical Center Utrecht, Netherlands

Oral
Patient-reported vaso-occlusive events, their associated pain severity, and impact of sickle cell disease on fatigue and quality of life: A real-world survey in the United States PS2179

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Oladipo Cole, M.D., University of Connecticut Health Center

Poster
Optimizing hydroxyurea therapy in sickle cell disease: Insights from metabolite detection, treatment response and clinical outcomes* PF1176

Friday, June 13, 2025, 6:30 – 7:30 PM CEST

Sigrid van der Veen, University Medical Center Utrecht, Netherlands

Poster
Ex-vivo activation of pyruvate kinase by tebapivat reduces sickling and red blood cell adhesion in sickle cell disease PS2170

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Minke Rab, M.D., Ph.D., University Medical Center Utrecht, Netherlands

Poster
Pyruvate Kinase Deficiency
Efficacy and safety of mitapivat in pediatric patients with pyruvate kinase deficiency who are regularly transfused: Results from the phase 3 randomized global placebo-controlled ACTIVATE-KidsT trial S296 Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Rachael F. Grace, M.D., MMSc; Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, Harvard Medical School Oral
Cardiac magnetic resonance observations in a patient with pyruvate kinase deficiency and beta-thalassemia trait treated with mitapivat – a case report PB3570 N/A Paolo Ricchi, M.D., Ph.D., Center for Rare Red Blood Cell Diseases, AORN A. Cardarelli, Naples, Italy Publication
Myelodysplastic Syndromes
PKM and PKLR mRNA expression in CD34+ cells derived from patients with myelodysplastic syndromes PB2748

N/A Erin Tsai, M.S., Agios Pharmaceuticals Publication
Other
SATISFY: Mitapivat in adults with erythrocyte membranopathies and congenital dyserythropoietic anemia type II: A EuroBloodNet, multicenter, single-arm, phase 2 study S297

Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Thomas Doeven, M.D., University Medical Center Utrecht, Netherlands

Oral
Red blood cell age distribution and metabolic features in hereditary spherocytosis, hereditary xerocytosis and congenital dyserythropoietic anemia – baseline results of exploratory analysis from the SATISFY study PS2199

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Richard van Wijk, Ph.D., University Medical Center Utrecht, Netherlands

Poster
PIEZO1 gain-of-function drives glycolytic imbalance in late-stage erythropoiesis: The potential of mitapivat therapy in dehydrated hereditary stomatocytosis PS2201 Saturday, June 14, 2025, 6:30 – 7:30 PM CEST Barbara Eleni Rosato, Ph.D., University of Naples, Italy Poster

*This investigator-sponsored trial is part of a larger project funded by Agios

Please refer to the EHA (Free EHA Whitepaper) 2025 online program for full session details and data presentation listings, and visit the Agios booth (#C04) onsite.

About PYRUKYND (mitapivat)
U.S. INDICATION
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.

U.S. IMPORTANT SAFETY INFORMATION
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.

Hepatocellular Injury in Another Condition: In patients with another condition treated with PYRUKYND at a higher dose than that recommended for patients with PK deficiency, liver injury has been observed. These events were characterized by a time to onset within the first 6 months of treatment with peak elevations of alanine aminotransferase of >5× upper limit of normal (ULN) with or without jaundice. All patients discontinued treatment with PYRUKYND, and these events improved upon treatment discontinuation.

Obtain liver tests prior to the initiation of PYRUKYND and monthly thereafter for the first 6 months and as clinically indicated. Interrupt PYRUKYND if clinically significant increases in liver tests are observed or alanine aminotransferase is >5x ULN. Discontinue PYRUKYND if hepatic injury due to PYRUKYND is suspected.

Adverse Reactions: The most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.

Drug Interactions:

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.

Please see full Prescribing Information for PYRUKYND.

On May 14, 2025 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported its abstract has been selected for a poster presentation at the 2025 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting (EHA) (Free EHA Whitepaper) being held June 12-15 in Milan, Italy (Press release, Karyopharm, MAY 14, 2025, View Source [SID1234653063]). The abstract contains data on selinexor monotherapy in a hard-to-treat, heavily pretreated myelofibrosis patient population from the Phase 2 XPORT-MF-035 trial.

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"We are encouraged by our new data in hard-to-treat myelofibrosis patients where we observed spleen volume reduction, symptom improvement, hemoglobin stabilization and evidence of disease modification with selinexor monotherapy, addressing all four hallmarks of the disease," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "This new data adds to our growing body of evidence highlighting selinexor’s potential in patients with myelofibrosis."

The accepted abstract and data highlights are below.

Abstract number: PS1821
Title: A study to evaluate single-agent selinexor versus physician’s choice in participants with previously treated myelofibrosis
Date/Time: Saturday, June 14, 18:30-19:30 CEST
Presenter: Alessandro Lucchesi, MD
Highlights

Data from the XPORT-MF-035 (NCT04562870) Phase 2, randomized, open-label trial of selinexor versus physician’s-choice (PC) in hard-to-treat patients with heavily pretreated myelofibrosis indicated signs of single-agent clinical activity with selinexor, including spleen volume reduction, hemoglobin stabilization, symptom improvement and evidence of disease modification.
Patients were randomized 1:1 to either selinexor monotherapy or PC. Selinexor was administered at 80 mg weekly for the first two cycles and then decreased to 60 mg weekly from cycle 3 onwards. An optional crossover was available for PC treated patients if they met predefined spleen progression criteria.
In total, 12 patients were randomized to the selinexor arm and 12 patients to the PC arm; 6 patients crossed over from PC to selinexor. Inclusive of crossover, spleen volume reduction of 25% or more (SVR25) at anytime was achieved in 8/12 (67%) efficacy evaluable selinexor treated patients versus 3/8 (38%) efficacy evaluable patients treated with PC. Spleen volume reduction of 35% or more (SVR35) at anytime was observed in 4/12 (33%) efficacy evaluable patients treated with selinexor versus 1/8 (13%) efficacy evaluable patients treated with PC.
Patients treated with selinexor had higher mean hemoglobin levels throughout the study duration and lower rates of red blood cell transfusions than those treated with PC.
Data on key cytokines that are relevant to myelofibrosis pathogenesis, symptom development, and anemia including IL-6, IL-8, TNFa, and hepcidin, demonstrated greater reductions at week 4 compared to baseline in patients treated with selinexor than patients treated with PC.
Most common (≥25% overall) treatment emergent adverse events (TEAEs) in the randomized arms were decreased weight (selinexor: 50%; PC: 50%), anemia (25%; 58%), asthenia (42%; 25%), nausea (33%; 25%), thrombocytopenia (33%; 25%) and upper respiratory tract infection (25%; 33%). Most common (≥15% in any arm) Grade 3+ TEAEs were anemia (17%; 58%), cardiac failure (0%; 17%), decreased appetite (17%; 0%) and nausea (17%; 0%). No treatment discontinuations due to TEAEs were observed in the selinexor arm.
About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in adult patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO/NEXPOVIO is marketed in these respective ex-U.S. territories by Karyopharm’s partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations

Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.