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Rigel Announces First Patient Enrolled in the Dose Expansion Phase of its Phase 1b Study of R289 in Patients with Lower-Risk MDS

On October 8, 2025 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, reported the first patient has been enrolled in the dose expansion phase of the ongoing Phase 1b study of R2891 in patients with relapsed or refractory (R/R) lower-risk myelodysplastic syndrome (MDS) (Press release, Rigel, OCT 8, 2025, View Source [SID1234656515]). R289 is Rigel’s potent and selective dual inhibitor of interleukin receptor-associated kinases 1 and 4 (IRAK1/4).

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"Today marks an important step in the evaluation of R289 for the treatment of patients with transfusion dependent lower-risk MDS, a disease with a persistent unmet need despite the availability of approved agents. In the dose expansion phase of this study, patients with transfusion dependent R/R lower-risk MDS will be randomized to receive a 500 mg R289 dose either once or twice daily," said Lisa Rojkjaer, M.D., Rigel’s chief medical officer. "The outcome of this phase of the study will be the selection of the recommended Phase 2 dose of R289 for future clinical studies. We remain grateful to our investigators for their continued support of our program."

Rigel’s open-label, Phase 1b study of R289 is evaluating the safety, tolerability, pharmacokinetics and preliminary activity in patients with R/R lower-risk MDS (NCT05308264). Enrollment in the dose escalation phase of the study was completed in July 2025, and the company expects to share updated data from the study later this year. In the dose expansion phase of the study, up to 40 patients will be randomized into dose levels of 500 mg once daily or 500 mg twice daily to determine the recommended Phase 2 dose (RP2D) for future development of R289. In addition, once the RP2D has been determined, an exploratory cohort of erythropoiesis-stimulating agent (ESA) R/R, or ineligible, lower-risk MDS patients will be evaluated at the RP2D.

R289 was previously granted Orphan Drug designation for the treatment of myelodysplastic syndromes and granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS by the FDA.

About R289
R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.

Libtayo® (cemiplimab-rwlc) Approved in the U.S. as First and Only Immunotherapy for Adjuvant Treatment of Cutaneous Squamous Cell Carcinoma (CSCC) with a High Risk of Recurrence After Surgery and Radiation

On October 8, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the U.S. Food and Drug Administration (FDA) has approved the PD-1 inhibitor Libtayo (cemiplimab-rwlc) as an adjuvant treatment for adult patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence after surgery and radiation (Press release, Regeneron, OCT 8, 2025, View Source [SID1234656514]). The FDA evaluated Libtayo under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in the treatment of serious conditions. An additional regulatory application is also under review in the European Union, with a decision expected by the first half of 2026.

"Patients whose CSCC is at a high risk of recurrence following surgery and radiation often have the poorest outcomes. Until now, we lacked options to help prevent a devastating recurrence and immunotherapy was only available for patients with advanced CSCC who were no longer candidates for curative surgery or curative radiation," said Vishal A. Patel, M.D., Associate Professor of Dermatology and of Medicine (Hematology/Oncology), George Washington University School of Medicine & Health Sciences and Director, Cutaneous Oncology Program, GW Cancer Center. "Many patients who undergo surgical resection of their CSCC are later found, on full pathological evaluation, to be at high risk of recurrence. As the first and only immunotherapy approved in the adjuvant setting, Libtayo represents a practice-changing opportunity for this patient population, backed by compelling data showcasing its ability to significantly improve disease-free survival."

The FDA approval is based on data from the pivotal Phase 3 C-POST trial investigating adjuvant Libtayo versus placebo in patients with CSCC at high risk of recurrence after surgery and radiation. Results from the study, which were published in the New England Journal of Medicine and presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting earlier this year, showed that Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death compared to placebo in patients with CSCC at high risk of recurrence after surgery and radiation (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.20-0.51; p<0.0001).

The safety profile of Libtayo as adjuvant treatment of patients with CSCC at high risk of recurrence after surgery and radiation is consistent with the known safety profile for Libtayo monotherapy in advanced cancers. The most common adverse reactions as a single agent in adjuvant CSCC at high risk of recurrence (≥10%, with a difference between arms of ≥3% compared to placebo) were rash, pruritus, and hypothyroidism. Serious adverse reactions occurred in 18% of patients and those that occurred in ≥1% of patients in the Libtayo arm were pneumonia (1.5%), rash (1.5%), diarrhea (1.5%), adrenal insufficiency (1%), and arrhythmia (1%).

"This approval provides patients with CSCC at high risk of disease recurrence following surgery and radiation a much-needed option, as Libtayo is the only immunotherapy to demonstrate efficacy in this setting," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. "Now with five FDA-approved indications, Libtayo is firmly established as a strong and versatile PD-1 inhibitor option for patients with a variety of cancers."

"CSCC is one of the most common skin cancers in the world, with an estimated 1.8 million cases diagnosed each year in the U.S. alone. While it can often be treated successfully with surgery and radiation, many patients face serious risk of advanced disease recurrences," said Samantha R. Guild, President, AIM at Skin Cancer Foundation. "This approval is wonderful news for people living with CSCC, and we commend Regeneron for its long-standing commitment to addressing needs in non-melanoma skin cancer through its pioneering research."

Regeneron is committed to helping patients who have been prescribed Libtayo access their medication. The company has launched Libtayo Surround, which offers financial and educational resources to help support patients throughout their treatment journey. For more information, patients can call 1-877-LIBTAYO (1-877-542-8296).

The approved supplemental Biologics License Application (sBLA) did not include Catalent Indiana, LLC as a filling site.

About Regeneron in Cancer
We aspire to turn revolutionary discoveries into medicines that can transform the lives of those impacted by cancer. Our team around the world is driven to solve the needs and challenges of those affected by one of the most serious diseases of our time.

Backed by our legacy of scientific innovation and a deep understanding of biology, genetics and the immune system, we’re pursuing potential therapies across more than 30 types of solid tumors and blood cancers. Our cancer strategy is powered by cutting-edge technologies and therapies that can be flexibly combined to investigate potentially transformative treatments for patients. Oncology assets in clinical development comprise nearly half of Regeneron’s pipeline, and include checkpoint inhibitors, bispecific antibodies and costimulatory bispecific antibodies. Our approved PD-1 inhibitor Libtayo serves as the backbone of many of our investigational combinations.

To complement our extensive in-house capabilities, we collaborate with patients, healthcare providers, governments, biopharma companies and each other to further our shared goals. Together, we are united in the mission to serve as a beacon of transformation in cancer care.

About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was invented using Regeneron’s proprietary VelocImmune technology. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. Libtayo has been approved by regulatory authorities in more than 30 countries in one or more indications, including for certain adult patients with advanced basal cell carcinoma (BCC), CSCC that is advanced or at high risk of recurrence, advanced non-small cell lung cancer (NSCLC) and advanced cervical cancer.

In the U.S., the generic name for Libtayo in its approved indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA. Outside of the U.S., the generic name of Libtayo in its approved indications is cemiplimab.  

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in trials as a monotherapy, as well as in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

U.S. FDA-approved Indications
Libtayo is a prescription medicine used to treat:

Adults with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC):
that has spread or cannot be cured by surgery or radiation, or
to help prevent CSCC from coming back if your CSCC is at high risk of coming back after it has been removed by surgery and radiation.
Adults with a type of skin cancer called basal cell carcinoma (BCC) when your BCC cannot be removed by surgery (locally advanced BCC) or when it has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with a HHI.
Adults with a type of lung cancer called non-small cell lung cancer (NSCLC).
LIBTAYO may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor does not have an abnormal "EGFR," "ALK," or "ROS1" gene.
LIBTAYO may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high "PD-L1," and your tumor does not have an abnormal "EGFR," "ALK," or "ROS1" gene.
It is not known if Libtayo is safe and effective in children. 

IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS 

What is the most important information I should know about LIBTAYO?
LIBTAYO is a medicine that may treat certain cancers by working with your immune system. LIBTAYO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, or chest pain
Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness
Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach-area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal
Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite
Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes
Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with LIBTAYO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising
Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: nausea, vomiting, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling
Rejection of a transplanted organ or tissue. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ or tissue transplant that you have had
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with LIBTAYO. Your healthcare provider will monitor you for these complications
Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with LIBTAYO. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with LIBTAYO if you have severe side effects.

Before you receive LIBTAYO, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ or tissue transplant, including corneal transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby
Females who are able to become pregnant:

Your healthcare provider will give you a pregnancy test before you start treatment
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this time
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO
are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of LIBTAYO when used alone to treat CSCC that has spread or cannot be cured by surgery or radiation, BCC or NSCLC include tiredness, muscle or bone pain, rash, diarrhea, and low levels of red blood cells (anemia).

The most common side effects of LIBTAYO when used alone to help prevent CSCC from coming back include rash and itching.

The most common side effects of LIBTAYO when used in combination with platinum-containing chemotherapy to treat NSCLC include hair loss, muscle or bone pain, nausea, tiredness, numbness, pain, tingling, or burning in your hands or feet, and decreased appetite.

These are not all the possible side effects of LIBTAYO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals at 1-877-542-8296.

NUCLIDIUM Presents Positive Phase I/II Results for First Copper-based PET Diagnostic in Neuroendocrine Tumors at EANM Congress 2025

On October 8, 2025 NUCLIDIUM AG a clinical-stage radiopharmaceutical company developing a proprietary copper-based theranostic platform, reported positive clinical data from the ongoing Phase I/II trial (NCT06455358) evaluating its novel copper-radiolabeled PET tracer, 61Cu-TraceNetTM ([61Cu]Cu-NODAGA-LM3) in patients with SSTR-positive gastroenteropancreatic and bronchopulmonary neuroendocrine tumors (GEP & BP-NETS) (Press release, NUCLIDIUM, OCT 8, 2025, https://nuclidium.com/nuclidium-presents-positive-phase-1-2-results-for-first-copper-based-pet-diagostic-in-neuroendocrine-tumors-at-eanm-congress-2025/ [SID1234656513]). Principal investigator Dr. Guillaume Nicolas, Deputy Head of Nuclear Medicine at the Department of Theragnostics at University Hospital Basel, Switzerland, presented the results in an oral session during the European Association of Nuclear Medicine (EANM) Congress in Barcelona, Spain.

The first-in-human, open-label, randomized, reader-blinded, Phase I/II study compared the safety, biodistribution, tumor uptake, and image quality of NUCLIDIUM’s copper-61-radiolabeled somatostatin receptor subtype 2 (SSTR2) antagonist, 61Cu-TraceNetTM with the standard of care gallium-68-labelled SSTR2 agonist, [68Ga]Ga-DOTA-TOC. In the first 22 patients with well-differentiated GEP and BP-NETs evaluated at the University Hospital Basel, 61Cu-TraceNET was well tolerated with no clinically significant adverse events reported. 61Cu-TraceNET showed a higher tumor uptake and tumor-to-background ratio and detected additional lesions in the liver and lungs. In a blinded analysis, independent readers rated the 61Cu-TraceNET image quality as superior compared to 68Ga-DOTATOC at both 1- and 3-hour imaging post-injection, supported by its 5.6-hour half-life, which enables broader distribution and delayed imaging. The image quality of 61Cu-TraceNET at 1- and 3-hours post-injection was assessed as equally good.

"Next-generation radiopharmaceuticals have the potential to transform the diagnosis and management of difficult-to-treat cancers. The first-in-human data with NUCLIDIUM’s novel copper-based diagnostic, 61Cu-TraceNETTM, show its excellent tumor specificity, improved image quality, and its ability to detect additional metastases," said Guillaume Nicolas, MD, PhD, Principal Investigator of the trial. "I am also encouraged by the safety, pharmacokinetic data, and the strong potential for 61Cu-TraceNETTM to support clinicians in the diagnosis in a range of SSTR2-positive tumors, including metastatic breast cancer, where better diagnostic approaches are urgently needed to improve treatment strategies."

Leila Jaafar, PhD, CEO and Co-Founder of NUCLIDIUM added "This rapidly generated first clinical data with 61Cu-TraceNETTM validates the potential of our copper-based platform and our ability to radiolabel an SSTR2 antagonist with high yield at room temperature for convenient patient diagnosis. With high specificity, low toxicity, and the potential to detect even the smallest primary and metastatic tumors early, 61Cu-TraceNET is well positioned to become a best-in-class diagnostic. We remain committed to rapidly advancing our copper-based theranostic pipeline to improve outcomes for patients across multiple cancer types with a focus on women’s health."

61Cu-TraceNETTM is the diagnostic component of NUCLIDIUM’s TraceNETTM program, targeting NETs and other SSTR-positive tumors such as metastatic breast cancer. A clinical trial of the corresponding therapeutic, 67Cu-TraceNET, is expected to start enrolling patients in 2026.

Bayer and Kumquat Biosciences initiate Phase I study with KRAS G12D inhibitor in patients with KRAS-mutated tumors

On October 8, 2025 Bayer and Kumquat Biosciences Inc., a clinical-stage biotech company founded by pioneers of targeting the KRAS pathway, reported the initiation of a Phase I clinical trial with KQB548 (BAY 3771249), an investigational inhibitor designed to treat KRAS G12D-mutated tumors, such as pancreatic, colorectal and lung cancer (Press release, Kumquat Biosciences, OCT 8, 2025, View Source [SID1234656511]). The first-in-human, dose-escalation study (NCT07207707) will evaluate the safety and preliminary efficacy of KQB548 (BAY 3771249) as a monotherapy in patients with KRAS G12D mutated tumors. KRAS mutations occur in nearly 25 percent of human cancers, yet the most prevalent and oncogenic KRAS variant (G12D) still lacks effective treatment options.

"Initiating clinical development of investigational KRAS G12D inhibitor KQB548 (BAY 3771249) marks an important milestone in our commitment to develop new medicines targeting highly relevant signaling pathways that promote tumor growth and survival," said Dominik Ruettinger, M.D., Ph.D., Global Head of Research and Early Development for Oncology at Bayer’s Pharmaceuticals Division. "Targeting KRAS has been considered quite challenging. We aim to deliver treatment options for patients with cancers driven by the KRAS G12D mutation. Through continued research innovation we can unlock the potential of precision oncology and improve the lives of people living with cancer."

KRAS G12D mutations are found most frequently in approximately 37 percent of pancreatic ductal adenocarcinoma (PDAC), 13 percent of colorectal cancer and 4 percent of non-small cell lung cancers. These mutations are often recognized as important targets for cancer treatment, and their detection paves the way for the creation of tailored therapies.

Despite recent scientific advancements, there are currently no effective treatments available that provide durable therapeutic benefits for most patients with KRAS-G12D-mutated cancers. Introducing the KRAS G12D inhibitor into clinical trials aims to address the long-standing unmet need.

"We are excited to initiate the clinical trial of our KRAS G12D inhibitor KQB548, which holds the prospect of transforming the KRAS G12D treatments for the deadly malignancies such as pancreatic, lung and colorectal cancers," said Dr. Nicolas Acquavella, Senior Vice President of Clinical Development and Corporate Alliance Management of Kumquat. "The speedy enrollment highlights our team’s execution capabilities and Kumquat’s long-standing commitment to delivering potentially life-changing medicines to cancer patients."

About KRAS G12D inhibitor (KQB548 – BAY 3771249)
KQB548 (BAY 3771249) is an investigational KRAS G12D inhibitor being developed to treat KRAS-mutated tumors, such as pancreatic, colorectal and lung cancer. KQB548 (BAY 3771249) is the lead program from the Bayer and Kumquat global exclusive license and collaboration in precision oncology. Kumquat received U.S. Food and Drug Administration (FDA) clearance of the investigational new drug (IND) for its KRAS G12D inhibitor in July 2025.

Karyopharm Announces Strategic Financing Transactions to Support Growth; Extends Cash Runway Into Second Quarter of 2026, Beyond Expected Top-Line Readout of Phase 3 SENTRY Trial in Myelofibrosis

On October 8, 2025 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that it has entered into comprehensive financing and capital structure transactions expected to provide the Company with $100 million of financial flexibility and additional capital, extending the Company’s cash runway into the second quarter of 2026 based on the Company’s current operating plans (Press release, Karyopharm, OCT 8, 2025, View Source,-Beyond-Expected-Top-Line-Readout-of-Phase-3-SENTRY-Trial-in-Myelofibrosis [SID1234656510]).

"Following the recent completion of enrollment of our Phase 3 SENTRY trial in myelofibrosis, we are excited to announce this strategic financing which is expected to provide us with the resources needed to deliver top-line data from this pivotal trial," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "I would like to thank our lenders, noteholders and equity investors for their ongoing support to strengthen our balance sheet, equitize near-term debt maturities and support our potentially transformational Phase 3 myelofibrosis program. We believe that selinexor plus ruxolitinib has the potential to be the first combination therapy approved for the treatment of myelofibrosis. By combining selinexor with the current standard of care, we have the potential to redefine the way people living with myelofibrosis are treated."

Each of the financing and capital structure transactions is expected to close on or around October 10, 2025 (Closing Date), subject to the satisfaction of customary closing conditions. The Company’s existing senior lenders have agreed to multi-faceted financing transactions with the following key components:

$67.5 million in financial flexibility and new capital consisting of $27.5 million in new term loan borrowings and new convertible notes, $25 million of near-term deferrals of interest and royalty payments, and a $15 million temporary reduction in the Company’s minimum liquidity covenant. In addition, holders of the Company’s convertible notes due 2029 have agreed to exchange $15 million of their notes for newly issued shares of common stock or pre-funded warrants in lieu thereof.
Holders of approximately $24.25 million aggregate principal amount of the Company’s senior unsecured convertible notes due October 15, 2025 have agreed to exchange their notes and accrued interest due thereon at a discount to par value for newly issued shares of common stock, or pre-funded warrants in lieu thereof, plus warrants to purchase shares of common stock.
In addition, the Company has entered into a securities purchase agreement for a private placement in which the Company agreed to sell 1,487,917 shares of common stock and accompanying warrants to purchase 1,317,771 shares of common stock with an exercise price of $6.64 per share. The warrants issued in the private placement will be exercisable on or before the 30th day following the public announcement of top-line results from the Company’s XPORT-EC-042 trial in endometrial cancer, which is anticipated in mid-2026. The private placement is expected to result in gross proceeds of approximately $8.75 million before deducting any offering expenses.

The Company intends to use the proceeds of the financing transactions to pay transaction expenses and for general corporate purposes, including to support the Company’s ongoing and planned clinical trial activities.

At closing of the financing transactions, the Company will issue an aggregate of 7,223,982 newly issued shares of common stock, newly issued pre-funded warrants to purchase an aggregate of 2,913,136 shares of common stock, and newly issued warrants to purchase an aggregate of 5,918,358 shares of common stock with an exercise price of $6.64 per share, a 15% premium to the Nasdaq minimum price. In addition, the Company will reduce the exercise price of outstanding warrants to purchase 3,068,417 shares from $16.50 per share to $6.64 per share. The financing transactions are intended to comply with Nasdaq rules, including being priced at the "minimum price" (as defined in the Nasdaq rules). Following consummation of the transactions, the Company expects to have an aggregate of 15,926,939 shares of common stock outstanding (assuming no exercise of any pre-funded warrants or warrants or conversions of any outstanding convertible notes).

Additional details on the financing transactions will be available in a Form 8-K that the Company will file with the United States Securities and Exchange Commission.

Preliminary Third Quarter 2025 Financial Results

Based on preliminary financial information, the Company expects total revenue, which includes license and royalty revenue from partners, to be in the range of $42 to $44 million and U.S. XPOVIO net product revenue to be approximately $32 million for the three months ended September 30, 2025.

Prior to the receipt of approximately $36 million of gross proceeds from the financing transactions, the Company expects to report that it had cash, cash equivalents, restricted cash and investments as of September 30, 2025 of approximately $46 million.

The financial information presented in this press release reflects the Company’s estimates with respect to total revenue, U.S. XPOVIO net product revenue and its cash balance and is based on currently available information, which is preliminary. The Company’s final results may vary from these preliminary estimates as a result of the completion of customary quarterly review procedures, including those conducted by the Company’s external auditors.

Endometrial Cancer Program

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. The Company continues to expect to report top-line data from this event-driven trial in mid-2026.

Ongoing Efforts to Further Enhance Liquidity and Maximize Value

The Company expects to continue exploring potential financing and strategic alternatives to enhance liquidity and maximize value with the assistance of its advisors, including its financial advisor Centerview Partners LLC.

Centerview Partners LLC and J. Wood Capital Advisors LLC acted as financial advisors to Karyopharm and Sidley Austin LLP acted as legal counsel to Karyopharm in connection with these transactions.

The offer and sale of the shares of common stock, pre-funded warrants, warrants, the New 2028 Notes, the New 2029 Notes or any other securities (including the shares of common stock issuable upon conversion of the New 2028 Notes, the New 2029 Notes and the shares of common stock issuable upon exercise of the warrants and pre-funded warrants issued in the financing transactions) are not being registered under the Securities Act, or any state securities laws. The shares of common stock, pre-funded warrants, warrants, the New 2028 Notes, the New 2029 Notes or any other securities (including the shares of common stock issuable upon conversion of the New 2028 Notes, the New 2029 Notes and the shares of common stock issuable upon exercise of the warrants and pre-funded warrants issued in the financing transactions) may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Securities Act and any applicable state securities laws.

This press release does not constitute an offer to sell or the solicitation of an offer to buy shares of common stock, pre-funded warrants, warrants, the New 2028 Notes, the New 2029 Notes or any other securities, nor shall there be any offer, solicitation or sale of shares of common stock, pre-funded warrants, warrants, the New 2028 Notes, the New 2029 Notes or any other securities (including the shares of common stock issuable upon conversion of the New 2028 Notes, the New 2029 Notes and the shares of common stock issuable upon exercise of the warrants and pre-funded warrants issued in the financing transactions) in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful.

About the Phase 3 SENTRY Trial

SENTRY (XPORT-MF-034; NCT04562389) is a Phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 109/L. Patients are randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline.

About Myelofibrosis

Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union1. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib. Patients treated with the most commonly prescribed JAK inhibitor often require blood transfusions, and more than 30% will discontinue treatment due to anemia.2 Anemia and transfusion dependence are strongly correlated with poor prognosis and shortened survival.3

1. Clarivate/DRG (2023)
2.. Palandri, F., Palumbo, G.A., Elli, E.M. et al. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis. Blood Cancer J. 11, 4 (2021).
3. Pardanani, A., & Tefferi, A. (2011). Prognostic relevance of anemia and transfusion dependency in myelodysplastic syndromes and primary myelofibrosis. Haematologica, 96(1), 8–10.

About the Phase 3 XPORT-EC-042 Trial

EC-042 (XPORT-EC-042; NCT05611931) is a global, Phase 3, randomized, double-blind clinical trial evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. The EC-042 trial is expected to enroll approximately 276 patients who will be randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The trial includes two patient populations, for which, the primary endpoint of progression free survival will be tested sequentially and the key secondary endpoint of overall survival will be evaluated: 1) a modified intent to treat population (mITT) that will include patients with either, a) TP53 wild-type tumors with proficient mismatch repair status (pMMR); or, b) TP53 wild-type tumors with deficient mismatch repair status (dMMR), who are medically ineligible to receive checkpoint inhibitors; and, 2) the trial’s original intent to treat (ITT) population, which will include all patients enrolled in the trial whose tumors are TP53 wild-type, regardless of MMR status. The mITT population is expected to include approximately 220 patients. In connection with the EC-042 trial, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOneCDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type.