On February 20, 2025 Myris Therapeutics emerged from stealth reported its strategic focus (Press release, Myris Therapeutics, FEB 20, 2025, View Source [SID1234650430]). Myris, formerly known as BioHybrid Solutions, has built on its history in enzyme bioconjugate development to emerge as a new Antibody Drug Conjugate (ADC) therapeutics company focused on the discovery and development of ultra-high Drug Antibody Ratio (DAR) ADCs. The first public release of Myris’ ADC capabilities will be presented at AACR (Free AACR Whitepaper) in Chicago, April 25-30, 2025.

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Myris Therapeutics has a novel pipeline of ultra-high DAR ADC oncology medicines, developed using the company’s deep expertise in polymer chemistry and cancer biologics. Myris’ technology enables the development of ADCs with DAR50-300, meaning Myris can put 50-300 copies of the drug payload per antibody which is 10-100x higher than current standards. "This dramatically expands the range of possible payloads and precision therapy opportunities. Moreover, there are many clinically-validated small molecules that have previously not been amenable to use in ADCs because of their pharmacology or therapeutic index," said Laura Benjamin, PhD, CEO of Myris Therapeutics. "We are advancing promising clinical candidates by utilizing innovative, yet proven, antibodies and payloads. Our emerging preclinical data suggest that we will see the expected improvement in efficacy and tolerability that the field so desperately needs."

Laura Benjamin, PhD, joined Myris’ Board in 2023 and stepped in as CEO in 2024 to lead the company’s shift to oncology. Prior to Myris, Laura was the CEO at OncXerna, where she raised >$100 million USD to advance clinical development of two oncology programs. Earlier positions included VP/CSO in oncology at Eli Lilly, Associate Professor in Pathology at Harvard Medical School, and Co-director of the Center for Vascular Biology at the Beth Israel Deaconess Medical School. Laura received her BA in Biology from Barnard College, Columbia University and her PhD in Molecular Biology from the University of Pennsylvania.

Myris Therapeutic’s predecessor company, BioHybrid Solutions, was founded to use sophisticated polymer chemistry to improve the druggability of therapeutic enzymes. The polymer technology remains central to Myris’ ultra-high DAR ADC capabilities and the company’s founders continue to play a leading role in Myris. Co-founder Krzysztof Matyjaszewski, PhD, from CMU is one of the leading figures in polymer chemistry world-wide and is a Director of Myris and active scientific advisor, co-founder Tonia Simakova, PhD, leads discovery research at Myris, and co-founder Alan Russell, PhD, currently VP of Large Molecule Discovery and Research Data Science at Amgen, is Chair of Myris’ Scientific Advisory Board. The company’s legacy programs are partnered and continue to advance rapidly towards the clinic. Pipeline success has allowed Myris to develop the technical capabilities needed to support the shift in focus to ultra-high DAR ADCs. Most notably, the lead program has been fully funded by the Department of Defense and has led to the successful nomination of a development candidate.

Under Laura Benjamin’s leadership, the team has been expanded to support the successful development of the ADC pipeline. Key advisors include biotech veteran Patrick Zweidler-McKay, MD, an experienced oncologist with over 11 years at MD Anderson, who spent 8 years developing ADCs at Immunogen before its acquisition by AbbVie, and decorated oncologist Pasi Janne, MD, currently Director for the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and Professor of Medicine at Harvard. In addition, the internal team has been strengthened by the addition of Becky Wolfe, a proven business and program leader in biopharma, as COO; Jeffrey S. Humphrey, MD, a seasoned industry oncologist, as CMO; and Bryant McLaughlin, PhD, an accomplished CMC scientist, as Head of CMC.

On February 20, 2025 Oxcia reported that the FDA (the United States Food and Drug Administration ) has granted ODD (orphan drug designation) to OXC-101 as a potential treatment option for patients with AML (acute myeloid leukemia) (Press release, Oxcia, FEB 20, 2025, View Source;utm_medium=rss&utm_campaign=oxc-101-has-been-granted-odd-status-by-the-fda-in-aml [SID1234650416]).

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OXC-101 is Oxcia’s lead clinical candidate, a first-in class mitotic MTH1 inhibitor with a unique dual mechanism of action. In short, OXC-101, fights cancer by taking advantage of one of the Achilles heels of cancer cells – the high endogenous oxidative stress and DNA damage. In preclinical studies, OXC-101 significantly prolongs survival and reduces tumor growth in AML disease models.

Clinical Phase 1 data in advanced hematological cancer patients is reassuring. Oxcia is now performing an expansion trial, a phase 1/2 study in a subpopulation (relapsed/recurrent AML), in combination with one of the standard treatments, idarubicin. The aim is to confirm the preliminary efficacy previously shown in AML to support further clinical development in a pivotal phase 2 trial that can be the base for regulatory fast-track approval.

Oxcia AB was in the beginning of 2023 awarded a grant of 3 million SEK by Swelife and Medtech4Health for this study. To ensure the recruitment of patients with this rare AML disease in a cost- and time-efficient manner, we are now adding additional clinical sites. Rigshospitalet in Denmark will be enrolled shortly. In addition, Bulgaria and Serbia will be added during 2025.

"We are delighted with the FDA’s decision to grant orphan drug designation to OXC-101 for AML. This is a significant milestone and underscores the significant unmet need for novel medicines and the unique approach by OXC-101. We believe OXC-101 holds potential to greatly improve treatment for patients who suffer from AML", says Ulrika Warpman Berglund, Oxcia’s CEO. We are presently preparing an application for ODD also with EMA (European Medicines Agency). Early engagement with the FDA and EMA is pivotal.

In the study we are also integrating precision medicine screening to help identify responders/non-responders. Precision medicine screening is a novel way of personalizing treatment for patients and thus identifying the best treatment strategy for individuals reducing unsuccessful treatments with unnecessary suffering and lack of effect.

Briefly about AML

Acute myeloid leukemia (AML) is an aggressive blood cancer associated with infection, anemia and bleeding. It is the most common acute leukemia in adults, accounting for more than 80% of the cases. In 2021, there were 162,200 incident cases of AML worldwide, and the number is forecasted to increase to 169,000 incident cases by 2027 (Datamonitor). Even though the overall survival rate among AML patients has been increasing in the past decades, it remains poor with an overall 5-year survival rate of 20% in selected subpopulations.

AML is a very heterogenous disease, which explains why classical intensive chemotherapy, constituting of a cytarabine /anthracycline backbone, remains the standard of care (SoC). The medical need is high. Although we have seen recent approvals for biomarker led AML subsets, the majority of patients are still in need of well-tolerated and effective novel therapies.

Briefly about Orphan Drug Designation

The FDA and EMA grant orphan status to products intended to treat, diagnose, or prevent a life-threatening rare disease or condition that affects fewer than five in 10,000 people in Europe, or under 200,000 people in the US, and with either no currently approved method of diagnosis, prevention, or treatment, or with significant benefit to those affected by the disease. Orphan drug designation provides certain benefits, including the potential for extensive marketing exclusivity following regulatory approval, reduction in regulatory fees and, in the case of EU, a centralized approval process.

On February 20, 2025 OS Therapies, Inc. (NYSE-A: OSTX), a clinical-stage biotechnology company advancing immunotherapies and targeted drug conjugates for cancer treatment, reported that it received a Notice of Allowance from the United States Patent & Trademark Office (USPTO) that a patent will be issued covering the manufacturing methods required for the OST-HER2 commercial product (Press release, OS Therapies, FEB 20, 2025, View Source [SID1234650434]). The USPTO granted a Patent Term Adjustment of 572 days, providing market exclusivity for the OST-HER2 commercial drug product into 2040. OS Therapies is preparing to initiate discussions with the United States Food & Drug Administration (FDA) following the successful treatment phase of its Phase 2b clinical trial in the prevention of recurrent, resected, lung metastatic osteosarcoma with a view towards submitting a Biologics Licensing Application (BLA) and gaining conditional or accelerated FDA approval in 2025. The Company recently completed a $7.1 million financing in January 2025 and has sufficient capital into mid-2026.

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OST-HER2 has already received rare pediatric disease (RPDD), fast-track (FTD) and orphan drug (ODD) designations from the US FDA for osteosarcoma. The Company intends to (1) focus on gaining FDA BLA approval for OST-HER2 in osteosarcoma in late 2025, (2) sell the Priority Review Voucher (PRV) it would receive from the FDA BLA approval prior to the September 30, 2026 PRV deadline to a larger pharmaceutical company at prevailing market prices (most recent PRV sale transaction was $150 million), (3) commercialize OST-HER2 in osteosarcoma and (4) then expand the clinical development of OST-HER2 into breast cancer and other larger solid tumor indications for additional revenue potential.

OST-HER2 has successfully completed a Phase 1 trial in adult patients with HER2 overexpressing cancers, primarily breast cancer patients. Preclinical breast cancer results with OST-HER2 showed:

78% reduction in tumor size (3mm for OST-HER2 treated vs. 14mm for control arm) in FVB/N HER2 transgenic mouse model of breast cancer treatment at day 75
33% prevention of breast cancer in OST-HER2 treated mice vs. 0% prevention of breast cancer in FVB/N HER2 transgenic model of breast cancer prevention at week 50
20% reduction of tumor size for OST-HER2 plus HER2-targeted antibody vs. HER2-targeted antibody alone Tg tumor regression model of breast cancer at day 42
65% reduction cellular concentration of metastatic cells for OST-HER2-treated mice compared with controls in brain metastasis model of primary breast cancer
The osteosarcoma treatment market was estimated at $1.2 billion in 2022 according to Data Bridge Market Research. The Company believes the market opportunity for OST-HER2 in the prevention of lung metastases in osteosarcoma is over $500 million. The breast cancer treatment market was estimated at $29.2 billion in 2023 and expected to grow to $53.7 billion by 2030 according to Grandview Research. The Company believes the market opportunity for OST-HER2 in the treatment of breast cancer exceeds $1 billion.

On February 19, 2025 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Karyopharm, FEB 19, 2025, View Source,-Announces-Update-to-Phase-3-XPORT-EC-042-Trial-and-Highlights-Recent-Company-Progress [SID1234650378]). In addition, Karyopharm highlighted select corporate milestones and provided an overview of its key clinical development programs.

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"In 2025, our teams remain focused on the transformative opportunity to redefine the standard of care in myelofibrosis, with top-line data from our Phase 3 SENTRY trial evaluating selinexor in combination with ruxolitinib on-track for the second half of 2025. We look forward to completing enrollment of our SENTRY trial in the first half of this year and leveraging our demonstrated commercialization capabilities in multiple myeloma to support a rapid launch, subject to approval," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "In endometrial cancer, today we announced our updated plans for our Phase 3 trial and intend to primarily focus on the TP53 wild-type pMMR population, which represents approximately 50% of all women with endometrial cancer, and expect to share top-line data in mid-2026."

Fourth Quarter 2024 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue for the year ended December 31, 2024 of $113 million, compared to $112 million for the year ended December 31, 2023. U.S. net product revenue for the fourth quarter of 2024 was $29 million, compared to $25 million for the fourth quarter of 2023.

Demand for XPOVIO was consistent in 2024 versus 2023, with demand growth in the second half of 2024 in both the community setting, which represents approximately 60% of XPOVIO net product revenue, and the academic setting, offsetting a decline in demand in the first half of the year due to an intensified competitive landscape.

XPOVIO net product revenue was impacted year-over-year by higher gross-to-net adjustments in 2024, driven primarily by increased 340B discounts and Medicare rebates.

Expanded global patient access for selinexor in 2024 with favorable reimbursement decisions in the United Kingdom, France, Italy, China and South Korea and additional regulatory approvals in UAE, Kuwait, China, Malaysia, Turkey, Thailand, and South Korea in various indications, increasing the number of countries where selinexor is now approved in more than 45 countries.
Research and Development (R&D) Highlights

Myelofibrosis

Updated the co-primary endpoint in the Phase 3 SENTRY trial (XPORT-MF-034; NCT04562389) to absolute mean change in total symptom score (Abs-TSS) following alignment with the U.S. Food and Drug Administration (FDA) and proactively increased the total sample size to approximately 350 patients to further increase the statistical powering. Abs-TSS measures the average improvement in symptom scores over 24 weeks relative to the baseline symptom score. Abs-TSS is viewed by many key opinion leaders (KOLs) and patient advocacy organizations as a more accurate assessment of symptom improvement in head-to-head clinical trials, such as SENTRY which is evaluating selinexor in combination with ruxolitinib in patients with JAK inhibitor (JAKi) naïve myelofibrosis versus ruxolitinib alone. Spleen volume reduction ≥35% (SVR35) at week 24 remains the other co-primary endpoint. These two co-primary endpoints will be tested sequentially starting with SVR35 followed by Abs-TSS.

Hosted an investor event with leading KOLs in October 2024 to discuss the change in the co-primary endpoint in the Phase 3 SENTRY trial to Abs-TSS and highlight the strength of the data from the Company’s Phase 1 trial in myelofibrosis. Data from the Company’s Phase 1 trial, evaluating the combination of selinexor 60 mg plus ruxolitinib in JAKi naïve myelofibrosis patients, demonstrated that 79% of patients in the intent to treat population (n=14) achieved SVR35 and an average Abs-TSS improvement of 18.5 points in the efficacy evaluable population (n=9), at week 24 relative to baseline. Acknowledging the small sample size, these data suggest that the combination is favorable compared to historical ruxolitinib monotherapy data which indicates that less than half of patients achieve SVR35 and an Abs-TSS improvement of 11 to 14 points1. As of the most recent data cut off, the safety profile remained consistent and no new safety signals were identified.

The Company continues to enroll patients into the 60 mg cohort of the Phase 2 SENTRY-2 trial of selinexor monotherapy in JAKi naïve patients with moderate thrombocytopenia (XPORT-MF-044; NCT05980806).
1Phase 3 MANIFEST trial. Rampal R, et al. ASH (Free ASH Whitepaper) 2023. Oral 628; Phase 3 TRANSFORM-1 trial Pemmaraju N, et al. ASH (Free ASH Whitepaper) 2023 abstract 620.

Endometrial Cancer

The Company is modifying the design of its Phase 3 XPORT-EC-042 trial evaluating selinexor as a maintenance-only therapy following systemic therapy versus placebo in patients with TP53 wild-type advanced or recurrent endometrial cancer. In late 2024 and early 2025, the Company engaged in communications with the FDA regarding the design adequacy of XPORT-EC-042 given the changing standard of care in endometrial cancer, particularly the approval of checkpoint inhibitors for patients with advanced or recurrent endometrial cancer regardless of mismatch repair status. In light of the FDA’s acknowledgement that the magnitude of benefit achieved from checkpoint inhibitors is less for patients with pMMR tumors than patients with dMMR tumors, consistent with the biology and mechanism of action of checkpoint inhibitors, the Company’s modifications include defining two patient populations for which the primary endpoint of progression free survival (PFS), tested sequentially, and key secondary endpoint of overall survival (OS) will be evaluated:

a modified intent to treat population (mITT) that will include patients with:

TP53 wild-type tumors with proficient mismatch repair status (pMMR); or,

TP53 wild-type tumors with deficient mismatch repair status (dMMR), who are medically ineligible to receive checkpoint inhibitors.

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 Company is increasing the trial sample size from 220 patients to approximately 276 patients, to ensure that the mITT population includes approximately 220 patients who are either: a) TP53 wild-type pMMR or b) TP53 wild-type dMMR and medically ineligible to receive a checkpoint inhibitor. The increase in sample size maintains sufficient power for the primary endpoint of PFS in the mITT population. To date, approximately 80% of patients enrolled meet the new eligibility definition for the mITT population.

The proposed modifications are intended to address certain of the FDA’s feedback regarding the evolving treatment landscape, including the approval of multiple checkpoint inhibitors for advanced/recurrent endometrial cancer patients with pMMR and/or dMMR tumors in 2023 and 2024.

Enrollment continues in the XPORT-EC-042 trial and, depending on the strength of the data, the Company intends to pursue regulatory approval. As a result of the proposed modifications, the Company now expects topline data in mid-2026.
Multiple Myeloma

Completed enrollment of the Phase 3 XPORT-MM-031 trial (EMN29; NCT05028348) of approximately 120 patients, leveraging the data published on selinexor 40 mg, pomalidomide and dexamethasone (SPd40) in 2024. The Phase 3 XPORT-MM-031 trial is being conducted in collaboration with the European Myeloma Network and is evaluating the all-oral combination SPd40 in patients with previously treated multiple myeloma who received an anti-CD38 in their immediate prior line of therapy. Pending ongoing engagement with regulatory agencies on the updated protocol and statistical plan, the Company intends to provide an update on this trial.
Anticipated Catalysts and Operational Objectives in 2025

Myelofibrosis

Announce completion of enrollment of the Phase 3 SENTRY trial evaluating selinexor in combination with ruxolitinib in JAKi naive myelofibrosis patients in 1H 2025.

Report preliminary data on a subset of participants in the 60 mg cohort from the Phase 2 SENTRY-2 trial evaluating selinexor as a monotherapy in patients with JAKi naïve myelofibrosis with moderate thrombocytopenia in 1H 2025.

Report top-line results from the Phase 3 SENTRY trial in 2H 2025.
Multiple Myeloma

Maintain the Company’s commercial foundation in the competitive multiple myeloma marketplace and drive increased XPOVIO revenues.

Continue global launches and reimbursement approvals for selinexor by partners in ex-U.S. territories.

Continue to follow patients that are enrolled in the Phase 3 XPORT-MM-031 (EMN29) trial. Pending ongoing engagement with regulatory agencies on the updated protocol and statistical plan, the Company intends to provide an update on this trial.
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.
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 $115 million to $130 million.

R&D and selling, general and administrative (SG&A) expenses to be in the range of $240 million to $255 million, which includes approximately $20 million of estimated non-cash stock-based compensation expense.

The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO net product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into the first quarter of 2026.2
2Excluding re-payment of $24.5 million aggregate principal amount of the Company’s remaining senior convertible notes due October 2025 (the 2025 Notes) and $25.0 million minimum liquidity covenant under the Company’s senior secured term loan due 2028. Taking into account the repayment of the 2025 Notes and the minimum liquidity covenant, Karyopharm expects its cash, cash equivalents and investments will be sufficient to fund its operations into the fourth quarter of 2025.

Full Year and Fourth Quarter 2024 Financial Results

Total revenue: Total revenue for the fourth quarter of 2024 was $30.5 million, compared to $33.7 million for the fourth quarter of 2023. Total revenue for the year ended December 31, 2024 was $145.2 million, compared to $146.0 million for the year ended December 31, 2023.

Net product revenue: Net product revenue for the fourth quarter of 2024 was $29.3 million, compared to $25.1 million for the fourth quarter of 2023. Net product revenue for the year ended December 31, 2024 was $112.8 million, compared to $112.0 million for the year ended December 31, 2023.

License and other revenue: License and other revenue for the fourth quarter of 2024 was $1.3 million, compared to $8.7 million for the fourth quarter of 2023. License and other revenue for the year ended December 31, 2024 was $32.4 million, compared to $34.0 million for the year ended December 31, 2023.

Cost of sales: Cost of sales for the fourth quarter of 2024 was $1.3 million, compared to $1.5 million for the fourth quarter of 2023. Cost of sales for the year ended December 31, 2024 was $6.0 million, compared to $4.9 million for the year ended December 31, 2023. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

R&D expenses: R&D expenses for the fourth quarter of 2024 were $33.3 million, compared to $39.4 million for the fourth quarter of 2023. R&D expenses for the year ended December 31, 2024 were $143.2 million, compared to $138.8 million for the year ended December 31, 2023. The increase in both periods was primarily due to increased clinical trial activity, partially offset by a reduction in headcount and contractors.

SG&A expenses: SG&A expenses for the fourth quarter of 2024 were $27.2 million, compared to $30.7 million for the fourth quarter of 2023. SG&A expenses for the year ended December 31, 2024 were $115.4 million, compared to $131.9 million for the year ended December 31, 2023. The decrease in both periods was primarily due to a reduction in headcount and contractors as well as lower commercial-related activities in connection with cost optimization efforts.

Interest income: Interest income for the fourth quarter of 2024 was $1.5 million, compared to $2.5 million for the fourth quarter of 2023. Interest income for the year ended December 31, 2024 was $7.4 million compared to $10.9 million for the year ended December 31, 2023, due to lower investment balances in 2024 as compared to 2023.

Interest expense: Interest expense for the fourth quarter of 2024 was $11.2 million, compared to $6.2 million for the fourth quarter of 2023. Interest expense for the year ended December 31, 2024 was $37.4 million, compared to $23.8 million for the year ended December 31, 2023. The increase in both periods was primarily due to the term loan and convertible debt that were issued in 2024.

Gain on extinguishment of debt and other income: Other income for the fourth quarter of 2024 was $10.1 million due to non-cash fair value remeasurements. The Company had immaterial other expense in the fourth quarter of 2023. Gain on extinguishment of debt and other income for the year ended December 31, 2024 was $73.1 million primarily due to the recognition of a $44.7 million non-cash gain on extinguishment of debt and $28.7 million non-cash fair value remeasurements, both of which related to the refinancing transactions that were completed in mid-2024. The Company had immaterial other expense for the year ended December 31, 2023.

Net loss: Karyopharm reported a net loss of $30.8 million, or $0.24 per basic and diluted share, for the fourth quarter of 2024, compared to a net loss of $41.8 million, or $0.36 per basic and diluted share, for the fourth quarter of 2023. Net loss included non-cash stock-based compensation expense of $3.9 million and $5.2 million for the fourth quarters of 2024 and 2023, respectively. Karyopharm reported a net loss of $76.4 million, or $0.63 per basic share and $0.93 per diluted share, for the year ended December 31, 2024, compared to a net loss of $143.1 million, or $1.25 per basic and diluted share, for the year ended December 31, 2023. Net loss included non-cash stock-based compensation expense of $18.4 million and $21.7 million for the years ended December 31, 2024 and 2023, respectively.

Cash position: Cash, cash equivalents, restricted cash and investments as of December 31, 2024 totaled $109.1 million, compared to $192.4 million as of December 31, 2023.

Conference Call Information

Karyopharm will host a conference call today, February 19, 2025, at 8:00 a.m. Eastern Time, to discuss the fourth quarter and full year 2024 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 patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in 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 February 20, 2025 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence (AI) company dedicated to developing cancer therapies and transforming the cost, pace, and timeline of oncology drug discovery and development, reported the publication of its PCT patent application (PCT/US2024/019851) covering a novel machine learning solution for predicting blood-brain barrier (BBB) permeability (Press release, Lantern Pharma, FEB 19, 2025, View Source [SID1234650395]). The application received a favorable PCT search report indicating no significant prior art, substantially strengthening its path to approval.

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The technology has demonstrated to-date exceptional performance in predicting BBB permeability across a wide range of chemical compounds, processing up to 100,000 molecules per hour with industry-leading accuracy. Notably, Lantern’s AI algorithms for BBB permeability prediction currently hold five of the top eleven positions on the Therapeutic Data Commons Leaderboard1. Lantern believes that this breakthrough capability can accelerate the drug development process by rapidly identifying compounds likely to cross the blood-brain barrier, a critical factor in developing treatments for central nervous system disorders and brain cancers. These identified compounds can then be accelerated and further developed by researchers in cancer drug development and other fields saving time and cost in early-stage molecular characterization.

"The publication of this PCT patent application represents a significant advancement in our AI-driven approach to drug development," stated Panna Sharma, Chief Executive Officer of Lantern Pharma. "This innovative technology not only enhances our internal development capabilities but also offers transformative potential for our partners and collaborators across the pharmaceutical industry. The system’s exceptional speed and accuracy in predicting BBB permeability positions Lantern at the forefront of CNS-targeted therapeutic development. We look forward to deploying this high-performing BBB model in collaboration with pharmaceutical partners and techbio-driven companies who seek to accelerate their development timelines while working with a partner committed to excellence, especially in the area of high-performing, predictive models for drug development."

The proprietary technology integrates advanced molecular representation techniques with synthetic data augmentation from features engineered from the chemical structure and bioactivity data which are then processed by leading-edge machine learning algorithms. Through integration with Lantern’s RADR AI platform, the system enables rapid and comprehensive assessment of both drug candidates and other molecules of interest for BBB permeability.

Lantern’s wholly-owned subsidiary, Starlight Therapeutics, intends to implement this technology to advance the development of STAR-001 and evaluate additional drug candidates. In addition, Lantern is actively expanding the system’s capabilities through the development of sophisticated sub-models that account for complex biological factors affecting BBB permeability. These enhancements are expected to further refine predictions by incorporating advanced features such as protein binding, active transport mechanisms, and disease-state modifications of the blood-brain barrier. This continued evolution of the technology demonstrates Lantern’s commitment to maintaining its leadership position in AI-driven drug development.

The PCT application enables Lantern to pursue patent protection in major markets worldwide, with potential coverage extending 20 years from the filing date. The company has initiated expedited review in the United States to accelerate market deployment.

This technological advancement reinforces Lantern’s position as an innovator in AI-driven drug development and strengthens its ability to develop more effective, targeted CNS cancer therapies. The company expects this development to significantly impact both its internal drug development pipeline and future collaboration opportunities.