On August 11, 2025 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported financial results for the second quarter ended June 30, 2025, and provided a business update (Press release, Protara Therapeutics, AUG 11, 2025, View Source [SID1234655074]).

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"As we look toward the second half of the year, we believe we are well positioned to continue to advance our pipeline of potentially transformative therapies for the treatment of patients with cancer and rare diseases," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We continue to execute on our ADVANCED-2 trial of TARA-002 in non-muscle invasive bladder cancer (NMIBC) and look forward to presenting interim results in the first quarter of 2026. In addition, we remain on track to dose the first patient in our THRIVE-3 registrational trial of IV Choline Chloride in patients dependent on parenteral support (PS) by the end of this quarter and expect to provide an interim update from the STARBORN-1 trial in pediatric patients with lymphatic malformations (LMs) in the fourth quarter of this year."

Recent Progress and Highlights

TARA-002 in NMIBC

The Company expects to report interim results from approximately 25 six-month evaluable NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are BCG-Unresponsive at a medical conference in the first quarter of 2026.
Following discussions with the U.S. Food and Drug Administration (FDA), the Company expects to provide an update on next steps in its BCG-Naïve program in the second half of 2025.
Protara continues to investigate subcutaneous dosing through priming and maintenance combined with intravesical dosing, as well as exploring combination treatments with TARA-002 in NMIBC patients with CIS.
IV Choline Chloride for Patients on Parenteral Support (PS)

The Company remains on track to dose the first patient in THRIVE-3, a registrational Phase 3 clinical trial, in the third quarter of 2025. In addition, following the recent clinical trial approval by the European Union Clinical Trials Regulation, the Company expects to begin enrollment across the EU in the coming months. THRIVE-3 is a seamless Phase 2b/3 trial with a dose confirmation portion (n=24) followed by a double-blinded, randomized, placebo-controlled portion to assess the efficacy and safety of intravenous (IV) Choline Chloride over 24 weeks in adolescents and adults on long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated (n=105). IV Choline Chloride was previously granted Fast Track designation by the FDA.
TARA-002 in LMs

Dosing remains ongoing in the Phase 2 STARBORN-1 trial of TARA-002 in pediatric patients with macrocystic and mixed cystic LMs and the Company intends to provide an interim update from the trial in the fourth quarter of 2025. The Company previously announced the completion of the study’s first safety cohort, in which TARA-002 showed promising results and was generally well-tolerated.
Corporate Update

In June 2025, Protara announced the appointment of William "Bill" Conkling as Chief Commercial Officer. He brings to Protara more than two decades of experience developing and commercializing novel cancer and rare disease therapeutics.
In June 2025, the Company announced it has been added as a member of the broad-market Russell 3000 Index as part of the annual reconstitution, effective at the open of U.S. equity markets on June 30, 2025.
Second Quarter 2025 Financial Results

As of June 30, 2025, unrestricted cash and cash equivalents and investments in marketable debt securities totaled $145.6 million. The Company expects its cash, cash equivalents, and investments in marketable debt securities will be sufficient to fund operations into mid-2027.
Research and development expenses for the second quarter of 2025 increased to $10.8 million from $6.4 million for the prior year period. The increase was primarily due to a $3.9 million increase in clinical trial activities for TARA-002 and IV Choline Chloride.
General and administrative expenses for the second quarter of 2025 increased to $5.8 million from $4.3 million for the prior year period. This increase was primarily due to an increase of $0.6 million in personnel-related expenses and $0.5 million in market development-related expenses.
For the second quarter of 2025, Protara incurred a net loss of $15.0 million, or $0.35 per share, compared with a net loss of $9.5 million, or $0.45 per share, for the same period in 2024.
About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma IL-6, IL-10, IL-12. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

About Lymphatic Malformations (LMs)

LMs are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of three years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.

About IV Choline Chloride

IV Choline Chloride is an investigational, intravenous phospholipid substrate replacement therapy in development for patients receiving parenteral support (PS). Choline is a known important substrate for phospholipids that are critical for healthy liver function that also play an important role in modulating gene expression, cell membrane signaling, brain development and neurotransmission, muscle function, and bone health. PS patients are unable to synthesize choline from enteral nutrition sources, and there are currently no available PS formulations containing choline. Approximately 78% of patients dependent on PS are choline-deficient and of those approximately 63% have some degree of liver dysfunction, which can lead to hepatic failure. Every year in the U.S. there are approximately 90,000 people who require PS at home and of those approximately 30,000 are on long-term PS. IV Choline Chloride has the potential to become the first U.S. Food and Drug Administration (FDA) approved IV choline formulation for PS patients. It has been granted Orphan Drug Designation by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term PN and been granted Fast Track Designation as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated. The U.S. Patent and Trademark Office has issued us a U.S. patent claiming a choline composition and a U.S. patent claiming a method for treating choline deficiency with a choline composition, each with a term expiring in 2041.

On August 11, 2025 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported financial and operating results for the second quarter ended June 30, 2025 (Press release, Olema Oncology, AUG 11, 2025, View Source [SID1234655073]).

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"Having achieved regulatory alignment on the selected dose for our pivotal palazestrant program during the second quarter, we are focused on accelerating enrollment in OPERA-01, which is on track for top-line data in the second half of 2026, and initiating the OPERA-02 combination trial in the frontline setting," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "Palazestrant’s demonstrated activity and combinability with multiple compounds offers the potential for it to become a best-in-class, backbone endocrine therapy for metastatic breast cancer. Our Phase 1 study of OP-3136, our potent and selective KAT6 inhibitor, is also generating strong investigator interest and patient enrollment, reinforcing our leadership in developing novel therapies for breast cancer and beyond."

Recent Progress

Selected 90 mg of once-daily palazestrant for Part 2 of the ongoing registrational OPERA-01 Phase 3 trial in second- and third-line (2/3L) estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) metastatic breast cancer, and for the OPERA-02 Phase 3 trial in combination with ribociclib in frontline ER+/HER2- metastatic breast cancer.
Continued enrollment in the Phase 1 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of OP-3136, as a monotherapy and in combination with fulvestrant and palazestrant, in participants with advanced solid tumors.
Anticipated Upcoming Events

Present mature data from the Phase 1b/2 study of palazestrant in combination with ribociclib in ER+/HER2- metastatic breast cancer at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in a presentation entitled "Palazestrant (OP-1250) plus ribociclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) advanced breast cancer (ABC)"
Initiate the OPERA-02 trial of palazestrant in combination with ribociclib in frontline metastatic breast cancer in Q3 2025.
Report initial clinical results for OP-3136 in 2026.
Report top-line data from OPERA-01 in the second half of 2026.
Second Quarter 2025 Financial Results
Cash, cash equivalents, and marketable securities of $361.9 million as of June 30, 2025.

Net loss for the quarter ended June 30, 2025 was $43.8 million, as compared to $30.4 million for the quarter ended June 30, 2024. The increase in net loss for the second quarter was related to a one-time milestone payment of $10 million made to Aurigene in conjunction with our KAT6 clinical development program as well as increased spending on research and development activities as a result of the ongoing late-stage clinical trials for palazestrant and the advancement of OP-3136, partially offset by higher interest income earned from marketable securities.

GAAP research and development (R&D) expenses were $43.9 million for the quarter ended June 30, 2025, as compared to $29.1 million for the quarter ended June 30, 2024. The increase in R&D expenses was primarily related to a one-time milestone payment of $10 million made to Aurigene as well as increased spending on clinical development-related activities as Olema continues to advance palazestrant through late-stage clinical trials, and the advancement of OP-3136.

Non-GAAP R&D expenses were $40.2 million for the quarter ended June 30, 2025, excluding $3.7 million non-cash stock-based compensation expense. Non-GAAP R&D expenses were $24.9 million for the quarter ended June 30, 2024, which excluded $4.2 million non-cash stock-based compensation expense. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release.

GAAP G&A expenses were $4.0 million for the quarter ended June 30, 2025, as compared to $4.4 million for the quarter ended June 30, 2024. The decrease in G&A expenses was primarily due to a decrease in non-cash stock-based compensation expense of $0.5 million.

Non-GAAP G&A expenses were $3.0 million for the quarter ended June 30, 2025, excluding $1.0 million non-cash stock-based compensation expense. Non-GAAP G&A expenses were $2.9 million for the quarter ended June 30, 2024, excluding $1.5 million non-cash stock-based compensation expense. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release.

On August 11, 2025 Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) ("Ligand") reported its intention to offer $400.0 million aggregate principal amount of convertible senior notes due 2030 (the "notes") in a private placement (the "offering") to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act"), subject to market conditions and other factors (Press release, Ligand, AUG 11, 2025, View Source [SID1234655072]). Ligand also expects to grant to the initial purchasers of the notes (the "initial purchasers") a 13-day option to purchase up to an additional $60.0 million aggregate principal amount of notes.

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The notes will be general unsecured, senior obligations of Ligand and will accrue interest payable semiannually in arrears on April 1 and October 1 of each year, beginning on April 1, 2026. The notes will mature on October 1, 2030, unless earlier converted, redeemed or repurchased. Upon conversion of the notes, Ligand will pay cash up to the aggregate principal amount of the notes to be converted and pay or deliver, as the case may be, cash, shares of Ligand’s common stock or a combination of cash and shares of Ligand’s common stock, at Ligand’s election, in respect of the remainder, if any, of Ligand’s conversion obligation in excess of the aggregate principal amount of the notes being converted. The interest rate, initial conversion rate, redemption or repurchase rights and other terms of the notes will be determined at the time of pricing of the offering.

Ligand expects to use a portion of the net proceeds from the offering to pay the cost of the convertible note hedge transactions described below (after such cost is partially offset by the proceeds to Ligand from the sale of the warrants in the warrant transactions described below). In addition, Ligand expects to use up to $30 million of the net proceeds from the offering to repurchase shares of its common stock from certain purchasers of the notes in privately negotiated transactions, as described below. Ligand intends to use the remaining net proceeds from the offering for general corporate purposes including investing in complementary businesses, companies, products and technologies, although Ligand has no present commitments or agreements to do so. If the initial purchasers exercise their option to purchase additional notes, Ligand expects to sell additional warrants to the option counterparties and use a portion of the net proceeds from the sale of the additional notes, together with the proceeds from the sale of the additional warrants, to enter into additional convertible note hedge transactions and the remaining net proceeds for general corporate purposes.

In connection with the pricing of the notes, Ligand expects to enter into convertible note hedge transactions (the "convertible note hedge transactions") with one or more of the initial purchasers or their respective affiliates and/or other financial institutions (the "option counterparties"). Ligand also expects to enter into warrant transactions (the "warrant transactions") with the option counterparties, pursuant to which Ligand will issue warrants to purchase common stock (the "warrants") to such option counterparties. The convertible note hedge transactions are expected generally to reduce the potential dilution to Ligand’s common stock upon any conversion of notes and/or offset any cash payments Ligand is required to make in excess of the principal amount of converted notes, as the case may be. However, the warrant transactions could separately have a dilutive effect on Ligand’s common stock to the extent that the market price per share of common stock exceeds the strike price of the warrants. If the initial purchasers exercise their option to purchase additional notes, Ligand expects to enter into additional convertible note hedge transactions and additional warrant transactions with the option counterparties.

In connection with establishing their initial hedges of the convertible note hedge transactions and the warrant transactions, Ligand expects the option counterparties or their respective affiliates to enter into various derivative transactions with respect to Ligand’s common stock and/or purchase shares of Ligand’s common stock concurrently with or shortly after the pricing of the notes. This activity could increase (or reduce the size of any decrease in) the market price of Ligand’s common stock or the notes at that time.

The option counterparties or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Ligand’s common stock and/or purchasing or selling shares of Ligand’s common stock or other securities of Ligand in secondary market transactions following the pricing of the notes and prior to the maturity of the notes (and are likely to do so in connection with any conversion, redemption or repurchase of the notes). This activity could also cause or avoid an increase or a decrease in the market price of Ligand’s common stock or the notes, which could affect a holder’s ability to convert its notes and, to the extent the activity occurs during any observation period related to a conversion of notes, it could affect the number of shares of Ligand’s common stock, if any, and value of the consideration, if any, that a holder will receive upon conversion of its notes.

In addition, Ligand expects to use up to $30 million of the net proceeds from the offering to repurchase shares of its common stock from certain purchasers of the notes in privately negotiated transactions effected through one of the initial purchasers or an affiliate thereof concurrently with the pricing of the notes. The price per share of Ligand’s common stock repurchased in such transactions is expected to equal the last reported price per share of Ligand’s common stock as of the date of the pricing of the notes. These repurchases could increase (or reduce the size of any decrease in) the market price of Ligand’s common stock prior to, concurrently with or shortly after the pricing of the notes, and could result in a higher effective conversion price for the notes. Ligand cannot predict the magnitude of such market activity or the overall effect it will have on the market price of the notes and/or the market price of Ligand’s common stock.

The notes and the warrants will only be offered to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act. The notes, the warrants, the shares of common stock into which the notes are convertible and the shares of common stock issuable upon exercise of the warrants have not been, and will not be, registered under the Securities Act or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States or to, or for the account or benefit of, U.S. persons, absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any securities, nor shall it constitute an offer to sell, solicitation of an offer to buy or sale of any securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On August 11, 2025 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the second quarter ended June 30, 2025 and highlighted progress on key clinical development programs (Press release, Karyopharm, AUG 11, 2025, View Source [SID1234655071]).

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"As we continue to seek potential financing and strategic alternatives to extend our cash runway and enhance liquidity, I am excited to announce that we are in our final weeks of enrolling our Phase 3 SENTRY trial and are on track to report top-line data from this pivotal trial in March 2026," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "Over the past seven years, we have led the development of a growing body of evidence supporting the role of XPO1 inhibition in myelofibrosis and are optimistic about selinexor’s potential in this disease. Completing enrollment is a very important step in our journey to potentially redefine the standard-of-care in myelofibrosis and provide a transformational opportunity for patients and our organization, pending positive data."

Second Quarter 2025 Highlights

XPOVIO Commercial Performance

U.S. net product revenue was $29.7 million in the second quarter of 2025 compared to $28.0 million in the second quarter of 2024.
Demand for XPOVIO was consistent in the second quarter of 2025 compared to the second quarter of 2024, with the community setting continuing to drive approximately 60% of overall net product revenue.
Expanded global patient access for selinexor is translating into growth in royalty revenue from Menarini, Antengene and other international partners. Royalty revenue increased 28% to $1.6 million in the second quarter of 2025 compared to the second quarter of 2024.
Research and Development (R&D) Highlights

Myelofibrosis

The Phase 3 SENTRY trial (XPORT-MF-034; NCT04562389) is nearing full enrollment and the Company expects new patient screening will be closed this week. SENTRY is targeting 350 patients for enrollment and is evaluating 60 mg once-weekly selinexor in combination with ruxolitinib compared to ruxolitinib plus placebo. The preliminary baseline characteristics for patients enrolled in SENTRY are representative of the intended patient population. In addition, preliminary blinded aggregate safety data from the first 61 patients with a median follow-up of greater than 12 months may suggest improvements in both hematologic and non-hematologic treatment emergent adverse events as compared to the Phase 1 data evaluating selinexor 60 mg weekly in combination with standard of care ruxolitinib in JAKi-naïve myelofibrosis patients, as well as historical ruxolitinib monotherapy data. The Company cautions that the preliminary baseline characteristics and preliminary blinded aggregate safety data may not be reflective of the actual top-line data.
Presented data from the XPORT-MF-035 (NCT04562870) Phase 2, randomized, open-label trial of selinexor versus physician’s-choice in hard-to-treat patients with heavily pretreated myelofibrosis (N=24) at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress. The data suggest the potential for single-agent clinical activity with selinexor, including spleen volume reduction, symptom improvement, hemoglobin stabilization, and evidence of disease modification. A copy of the poster that was presented at EHA (Free EHA Whitepaper), titled "A Study to Evaluate Single-Agent Selinexor Versus Physician’s Choice in Participants With Previously Treated Myelofibrosis" is available under "Publications and Presentations" in the Investor section of the Company’s website.
The Company continues to enroll JAKi-naïve myelofibrosis patients with moderate thrombocytopenia (defined as having platelet counts between 50,000 and 100,000) in the selinexor 60 mg cohort of the Phase 2 SENTRY-2 trial (XPORT-MF-044; NCT05980806). The Company plans to amend the protocol for SENTRY-2 to also include patients with platelet counts above 100,000, which will expand the number of patients that are eligible to participate in the trial. Approximately 10% to 15% of patients with myelofibrosis have platelet counts between 50,000 and 100,0001. The Company expects to report top-line data from all patients in the 60 mg cohort with at least 24 weeks of follow-up in 2026.
1 Tremblay et al. Thrombocytopenia in Patients With Myelofibrosis: A Practical Management Guide, Clinical Lymphoma Myeloma and Leukemia Vol 22 Dec 2022

Endometrial Cancer

Enrollment continues in the Phase 3 XPORT-EC-042 (NCT05611931) trial evaluating selinexor as a maintenance-only therapy following systemic therapy versus placebo in patients with TP53 wild-type advanced or recurrent endometrial cancer.
Multiple Myeloma

Enrollment of approximately 120 patients in the Phase 3 XPORT-MM-031 trial (EMN29; NCT05028348) was completed in the fourth quarter of 2024. The trial is being conducted in collaboration with the European Myeloma Network and is evaluating the all-oral combination of selinexor 40 mg, pomalidomide and dexamethasone (SPd40) in patients with previously treated multiple myeloma who received an anti-CD38 in their immediate prior line of therapy.
Anticipated Catalysts and Operational Objectives

Myelofibrosis

The Company expects new patient screening will be closed for the Phase 3 SENTRY trial this week with top-line data expected in March 2026.
Multiple Myeloma

Maintain the Company’s commercial foundation in the increasingly competitive multiple myeloma marketplace and drive increased XPOVIO revenues.
Continue to support global launches by our partners following regulatory and reimbursement approvals for selinexor in ex-U.S. territories.
Continue to follow patients that are enrolled in the Phase 3 XPORT-MM-031 (EMN29) trial. The Company expects to report top-line data from this event-driven trial in the first half of 2026.
Endometrial Cancer

Continue to enroll patients into the Phase 3 XPORT-EC-042 trial of selinexor as a maintenance monotherapy for patients with TP53 wild-type advanced or recurrent endometrial cancer. The Company expects to report top-line data from this event-driven trial in mid-2026.
2025 Financial Outlook

Based on its current operating plans, Karyopharm expects the following for full year 2025:

Total revenue to be in the range of $140 million to $155 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners.
U.S. XPOVIO net product revenue to be in the range of $110 million to $120 million.
R&D and selling, general and administrative (SG&A) expenses to be in the range of $240 million to $250 million.
The Company expects its existing liquidity, including the revenue it expects to generate from XPOVIO net product sales and its license agreements, will be sufficient to fund its planned operations to the maturity of its senior convertible notes due October 2025 (Remaining 2025 Notes). Excluding the $24.5 million Remaining 2025 Notes maturity and its $25.0 million minimum liquidity covenant, the Company expects it would have sufficient liquidity to fund planned operations into January 2026. The Company, with the assistance of its advisors, including its financial advisor Centerview Partners, is exploring potential financing and strategic alternatives to enhance liquidity and maximize value.
Second Quarter 2025 Financial Results

Total revenue: Total revenue for the second quarter of 2025 was $37.9 million, compared to $42.8 million for the second quarter of 2024.

Net product revenue: Net product revenue for the second quarter of 2025 was $29.7 million, compared to $28.0 million for the second quarter of 2024.

License and other revenue: License and other revenue for the second quarter of 2025 was $8.2 million, compared to $14.8 million for the second quarter of 2024. The decrease was primarily attributable to $6.0 million of non-recurring license-related revenue recognized during the second quarter of 2024.

Cost of sales: Cost of sales for the second quarter of 2025 was $1.1 million, compared to $1.5 million for the second quarter of 2024. Cost of sales reflects the costs of XPOVIO units sold and the costs of products sold to our partners.

R&D expenses: R&D expenses for the second quarter of 2025 were $32.8 million, compared to $38.4 million for the second quarter of 2024. The decrease was due to a reduction in personnel costs and stock-based compensation costs primarily due to a reduction in headcount and contractors, coupled with lower clinical trial and related costs due to the reduced scope of our Phase 3 multiple myeloma trial.

SG&A expenses: SG&A expenses for the second quarter of 2025 were $28.5 million, compared to $31.1 million for the second quarter of 2024. The decrease was primarily due to the realization of previously implemented cost reduction initiatives.

Interest income: Interest income for the second quarter of 2025 was $0.6 million, compared to $1.9 million for the second quarter of 2024. The decrease was due to a lower cash and investments balance quarter-over-quarter.

Interest expense: Interest expense for the second quarter of 2025 was $11.2 million, compared to $8.9 million for the second quarter of 2024. The increase was related to a full quarter of interest on the term loan and convertible debt that were issued in the second quarter of 2024.

Gain on Extinguishment of Debt and Other (expense) income: Other expense for the second quarter of 2025 was $2.2 million compared to $14.3 million of other income for the second quarter of 2024. The change is attributable to recurring non-cash fair value remeasurements related to the refinancing transactions that were completed in the second quarter of 2024. The refinancing transactions also resulted in a $44.7 million gain on extinguishment of debt during the second quarter of 2024.

Net (loss) income: Karyopharm reported a net loss of $37.3 million, or $4.32 net loss per basic and diluted share, for the second quarter of 2025, compared to net income of $23.8 million, or $2.26 net income per basic share and $2.97 net loss per diluted share, for the second quarter of 2024. Net (loss) income included non-cash stock-based compensation expense of $3.8 million and $5.4 million for the second quarters of 2025 and 2024, respectively.

Cash position: Cash, cash equivalents, restricted cash and investments as of June 30, 2025 totaled $52.0 million, compared to $109.1 million as of December 31, 2024.

Conference Call Information

Karyopharm will host a conference call today, August 11, 2025, at 8:00 a.m. Eastern Time, to discuss the second quarter 2025 financial results, the financial outlook for 2025 and to provide other business updates. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company’s website. An archived webcast will be available on the Company’s website approximately two hours after the event.

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.

On August 11, 2025 IO Biotech (Nasdaq: IOBT) reported topline results from the pivotal Phase 3 trial of its investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine, Cylembio (imsapepimut and etimupepimut, adjuvanted) (Press release, IO Biotech, AUG 11, 2025, View Source [SID1234655070]). The trial evaluated Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), vs. pembrolizumab alone as a first-line treatment in 407 patients with unresectable or metastatic (advanced) melanoma. In the study, Cylembio plus pembrolizumab demonstrated clinical improvement in progression free survival compared to pembrolizumab alone, but statistical significance was narrowly missed on the primary endpoint.

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"In this study, we observed a highly encouraging improvement in progression free survival and consistent trend in overall survival in patients treated with Cylembio," said Mai-Britt Zocca, PhD, president and chief executive officer of IO Biotech. "The magnitude and durability of clinical effect observed consistently across subgroups supports our confidence in Cylembio and its potential as a treatment for advanced melanoma patients. We look forward to engaging with the FDA to determine a potential path to approval based on these data."

The randomized, open-label study enrolled 407 patients across more than 100 sites worldwide. Patients received either Cylembio in combination with pembrolizumab (n=203) or pembrolizumab alone (n=204). The primary endpoint was PFS as assessed by a blinded independent review committee per RECIST v1.1. The early and sustained separation of PFS curves demonstrated an improvement with a hazard ratio of 0.77 [95% CI: 0.58-1.00; p=0.056; threshold for significance p≤0.045]. Based on an intent-to-treat analysis, patients in the study treated with Cylembio in combination with pembrolizumab achieved 19.4 months of median progression free survival compared to 11.0 months in patients treated with pembrolizumab alone.

Although not yet mature, a trend toward an improvement in overall survival was also observed [HR 0.79 (95% CI: 0.57-1.10)]; the company expects OS to mature over the next six to nine months.

Improvement in PFS was achieved across virtually all subgroups, including those with poor prognostic factors, with a profound effect in patients with PD-L1 negative tumors treated with Cylembio plus pembrolizumab (n=67) compared to patients treated with pembrolizumab monotherapy (n=63), HR: 0.54 (CI 0.35-0.85) (nominal p=0.006), with mPFS of 16.6 months vs. 3.0 months, respectively. Additionally, in a post hoc analysis of patients enrolled in this study without prior anti-PD-1 treatment (n=371), patients treated with Cylembio plus pembrolizumab achieved improvement in PFS compared to patients treated with pembrolizumab monotherapy, HR: 0.74 (CI 0.56-0.98) (nominal p=0.037), with mPFS of 24.8 months vs. 11.0 months, respectively.

The combination was well tolerated, with no new safety signals observed. Injection site reactions, which were transient and resolved on treatment, were the most commonly reported adverse events in the combination arm, with 56% of patients receiving Cylembio plus pembrolizumab reporting an event.

"In this study, patients treated with Cylembio in combination with pembrolizumab have achieved the longest median PFS ever observed in a Phase 3 clinical study in advanced melanoma, and in the PD-L1 negative population, patients achieved a remarkable 16.6 months of median PFS, compared to 3.0 months in patients treated with pembrolizumab alone," said Omid Hamid, MD, Director, Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate. "The significant benefit seen across patients with poor prognostic factors, including PD-L1 negative patients, cannot be overlooked. Given the notable safety profile and the strong clinical effect observed with Cylembio, as well as the unmet need in advanced melanoma patients, Cylembio, if approved, has the potential to become a new standard of care for patients with advanced melanoma."

"These data show the potential of a therapeutic cancer vaccine in patients with metastatic melanoma," said Jessica Hassel, MD, Professor at the Department of Dermatology and National Center for Tumor Diseases at the University Hospital Heidelberg, Germany, and lead enrolling investigator for the Phase 3 trial. "We were thrilled to play such an important part in this study and to have had the ability to offer our patients an investigational therapy that potentially offers improvements in PFS while not adding significant systemic toxicity."

"Delaying progression and improving survival is the ultimate treatment goal for patients and although overall survival is not yet mature, the trend we are seeing in OS with separation of the curves is encouraging, with a consistent PFS clinical improvement and OS trend favoring the combination arm across virtually all subgroups, with no new safety signals or significant additional systemic toxicity," said Qasim Ahmad, MD, chief medical officer of IO Biotech. "We are deeply grateful to the patients for their participation in this study, as well as to investigators and study coordinators whose dedication and collaboration brings us one step closer to delivering a new treatment option to patients in need."

"Since reporting the positive outcome of our Phase 1/2 study (MM1636) in a similar patient population, we have been eagerly awaiting these results supporting the activity of Cylembio combined with an anti-PD-1 in patients with advanced melanoma," said Inge Marie Svane, MD, PhD, Professor, Director of the National Center for Cancer Immune Therapy (CCIT) at the Copenhagen University Hospital, Herlev and Principal Investigator in the Phase 3 trial. "These data provide evidence that a therapeutic cancer vaccine can improve progression free survival in patients with metastatic disease."

Based on these results, IO Biotech plans to meet with the United States (US) Food and Drug Administration (FDA) this fall to discuss the totality of data and determine next steps for submission of a Biologics License Application (BLA) for the treatment of advanced melanoma. Additionally, the company plans to present more detailed results from the IOB-013 study at an upcoming medical meeting.

Conference Call and Webcast Information

IO Biotech management will hold a conference call and webcast today at 8:30 a.m. ET to discuss these clinical data results. Participants can register for the live webcast here. The live webcast and replay will be available through IO Biotech’s website here.

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

IOB-013/KN-D18 (ClinicalTrials.gov: NCT05155254) was 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. Enrollment in the trial was completed by December 2023 with a total of 407 patients enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study was progression free survival. 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. The company reported topline results from this trial in the third quarter of 2025. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab.

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 Phase 3 trial was completed rapidly by December 2023 with topline results from this trial reported in the third quarter of 2025. Enrollment in the two ongoing company-sponsored Phase 2 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 (known as MSD outside of the US and Canada).