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 19, 2025 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company entering a pivotal Phase 3 trial of its DNA-mediated immunotherapy, reported new translational data from ongoing analyses of results from the Company’s Phase 2 OVATION 2 Study of IMNN-001, its investigational interleukin-12 (IL-12) immunotherapy based on the company’s proprietary TheraPlas technology, for the treatment of newly diagnosed advanced ovarian cancer (Press release, IMUNON, FEB 19, 2025, View Source [SID1234650377]). Results demonstrated a 20% increase in IL-12 levels in women treated with IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus standard-of-care (SoC) neoadjuvant and adjuvant chemotherapy (NACT) compared to IL-12 levels in women treated with IMNN-001 (79 mg/m2).

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"These new data from the OVATION 2 Study confirm what we saw in the Phase 1 study and build on the robust body of evidence supporting the safety and strong overall survival results achieved with IMNN-001. These data also give us new levels of insight confirming the potential of our TheraPlas technology platform," said Stacy Lindborg, Ph.D., president and chief executive officer of IMUNON. "We are especially pleased that we continue to observe a highly positive benefit-risk profile of IMNN-001, the first immunotherapy to achieve clinically effective progression-free and overall survival in advanced ovarian cancer in conjunction with chemotherapy. We look forward to advancing this program to a Phase 3 pivotal trial, which remains on track to start this quarter."

In this analysis increases in IL-12 levels were sampled in the peritoneal fluid cavity, which is the primary tumor microenvironment. Little to no changes were observed in the systemic blood stream of treated patients. In addition, the rise in IL-12 levels was accompanied by local increases in interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), key downstream anti-cancer immune cytokines. Results showed no reports of serious immune-related adverse events including cytokine release syndrome.

"The increases in levels of IL-12 and positive downstream effects on IFN-γ and TNF-α indicate that IMNN-001 treatment is having a broad impact on important cancer-fighting cytokines and effectively targeting the tumor microenvironment with limited to no systemic toxicities," said Premal H. Thaker, M.D., Interim Chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, and the OVATION 2 Study Chair. "I look forward to hopefully seeing these remarkable results from the OVATION 2 Study replicated in a Phase 3 trial, which would further validate the significant potential of IMNN-001 to be transformative for the current standard of care for women with newly diagnosed advanced ovarian cancer."

In December 2024, IMUNON reported continued strong improvement in overall survival data from the Phase 2 OVATION 2 Study, demonstrating an improvement in median overall survival of 13 months following treatment with IMNN-001 (100 mg/m2) plus SoC NACT compared to SoC alone. More than one-third of patients in the trial survived more than 36 months from the point of study enrollment, with 62% of those surviving patients from the IMNN-001 treatment arm and 38% from the SoC arm. More than 10% of trial participants have reached 48 months or beyond.

Also in December 2024, IMUNON announced the outcome of an End-of-Phase 2 in-person meeting with the U.S. Food and Drug Administration (FDA), supporting the advancement of IMNN-001 for the treatment of advanced ovarian cancer into a Phase 3 pivotal study. IMUNON remains on track to initiate a Phase 3 pivotal trial of IMNN-001 using the selected 100 mg/m2 dose in the first quarter of 2025.

About the Phase 2 OVATION 2 Study

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare NACT plus IMNN-001 versus standard-of-care NACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to NACT. As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer. IMUNON previously reported positive results from the recently completed Phase 2 OVATION 2 Study, which assessed IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin compared to standard-of-care NACT alone in 112 patients with newly diagnosed advanced ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

On February 19, 2025 Genmab A/S (Nasdaq: GMAB) reported that its Chief Financial Officer Anthony Pagano and Chief Development Officer Judith Klimovsky will participate in a fireside chat at the 45th Annual TD Cowen Health Care Conference in Boston, Massachusetts at 1:50 PM EST (7:50 PM CET) on March 3, 2025 (Press release, Genmab, FEB 19, 2025, View Source [SID1234650376]). A webcast of the fireside chat will be available on Genmab’s website at View Source

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On February 19, 2025 Epitopea, a transatlantic cancer immunotherapeutics company developing accessible, off-the-shelf RNA-based immunotherapies, reported a license and research collaboration agreement with MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA) to identify CryptigenTM tumor-specific antigens (TSAs) in an undisclosed solid tumor (Press release, Epitopea, FEB 19, 2025, View Source [SID1234650375]). CryptigenTM TSAs are shared, non-mutated, aberrantly expressed antigens that are derived from what were thought to be non-coding regions of the genome or "junk DNA".

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Under the terms of the agreement, Epitopea will deploy its proprietary CryptoMapTM platform to identify and provide novel, immunogenic CryptigenTM TSAs for a prespecified tumor type. MSD will have the exclusive right to develop and commercialize therapeutics derived from the collaboration. In return Epitopea will receive an undisclosed upfront payment and is eligible for milestone payments with the potential to total up to $300 million per product.

"Epitopea has been at the forefront of identifying CryptigenTM TSAs, whose intratumor shared nature across patients has made them ideal targets for the development of off-the-shelf immunotherapies," commented Alan C. Rigby, Epitopea’s CEO. "At Epitopea we continue to accelerate the development of our preclinical pipeline as we transition to a clinical-stage company on the ‘heels’ of our recent, oversubscribed, pre-Series A financing. We believe that this strategic collaborative relationship with MSD, a leader in immunotherapy therapeutic development, provides us with an additional opportunity to validate the potential impact of these differentiated tumor specific antigens. We are thrilled to collaborate with MSD as our teams collectively look to impact the lives of patients with cancer by helping to improve outcomes."

"Despite the remarkable progress made in cancer treatment over the past decade, more therapeutic options are needed," said George Addona, senior vice president, discovery, preclinical development and translational medicine, Merck Research Laboratories. "We continue to explore new ways to build upon our strong foundation in immuno-oncology and look forward to collaborating with the Epitopea team."

"Having supported the company since its formation, we are thrilled that Epitopea’s next-generation antigen discovery platform will be leveraged in this license and research collaboration agreement with MSD, a leading biopharmaceutical company in the immuno-oncology space. This partnership provides strong validation for Epitopea’s unique capabilities and the potential to help develop breakthrough immunotherapies for cancer patients with the highest unmet need," added Michael Anstey, Partner at Cambridge Innovation Capital.

On February 19, 2025 Charles River Laboratories International, Inc. (NYSE: CRL) reported its results for the fourth quarter and full-year 2024 and provided guidance for 2025 (Press release, Charles River Laboratories, FEB 19, 2025, View Source [SID1234650374]). For the quarter, revenue was $1.00 billion, a decrease of 1.1% from $1.01 billion in the fourth quarter of 2023.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The impact of foreign currency translation reduced reported revenue by 0.1%, and an acquisition contributed 0.9% to consolidated fourth-quarter revenue. A divestiture reduced reported revenue by 0.1%. Excluding the effect of these items, revenue declined 1.8% on an organic basis. On a segment basis, organic revenue growth in the Manufacturing Solutions (Manufacturing) segment was more than offset by lower revenue in the Discovery and Safety Assessment (DSA) and Research Models and Services (RMS) segments.

In the fourth quarter of 2024, the GAAP operating margin decreased to (16.7)% from 13.1% in the fourth quarter of 2023. The primary driver of the GAAP decrease was a non-cash goodwill impairment of $215.0 million in the fourth quarter of 2024 related to the Biologics Solutions reporting unit, which includes the Biologics Testing and CDMO businesses. On a non-GAAP basis, the fourth-quarter operating margin increased to 19.9% from 19.1%, due primarily to higher revenue and operating income in the Manufacturing segment and lower unallocated corporate costs.
On a GAAP basis, the net loss available to common shareholders for the fourth quarter of 2024 was $(215.7) million, or $(4.22) per share, a decrease from net earnings of $187.1 million, or $3.62 per diluted share, for the same period in 2023. The GAAP decreases were primarily driven by the non-cash goodwill impairment, which totaled $4.20 per share, as well as a loss of $0.32 per share on certain venture capital and other strategic investments. This compares to a gain of $2.04 per share on certain venture capital and other strategic investments in the fourth quarter of 2023, which included a gain on our original strategic investment in Noveprim Group.
On a non-GAAP basis, net income was $136.6 million for the fourth quarter of 2024, an increase of 7.4% from $127.2 million for the same period in 2023. Fourth-quarter diluted earnings per share on a non-GAAP basis were $2.66, an increase of 8.1% from $2.46 per share for the fourth quarter of 2023. The increases in non-GAAP net income and earnings per share were driven by higher operating income, as well as favorable below-the-line items, including reductions in the tax rate, interest expense, and diluted shares outstanding.
James C. Foster, Chair, President and Chief Executive Officer, said, "Throughout 2024, we have launched initiatives to generate more revenue, aggressively reduce costs, and further strengthen our business. As we move into 2025, we see many of our global biopharmaceutical clients continuing to move forward with their restructuring and pipeline reprioritization activities, which are expected to constrain early-stage spending by many of these clients again in 2025. We believe these trends are stabilizing, and therefore, our view of the global biopharmaceutical demand environment remains unchanged. In addition, small and mid-sized biotechnology clients continued to benefit from a more favorable funding environment in 2024, and we expect biotechnology demand trends will be stable to slightly improved this year."

"During this period of softer demand, we remain committed to executing on our revenue and cost-savings initiatives and protecting shareholder value. We are taking decisive actions to emerge from this period as a stronger, leaner, and more profitable company, and an even more responsive partner for our clients," Mr. Foster concluded.

Fourth-Quarter Segment Results
Research Models and Services (RMS)
Revenue for the RMS segment was $204.3 million in the fourth quarter of 2024, an increase of 4.3% from $195.8 million in the fourth quarter of 2023. The Noveprim acquisition in November 2023 contributed 4.8% to fourth-quarter RMS reported revenue, and the impact of foreign currency translation reduced revenue by 0.1%. Organic revenue decreased by 0.4%, due primarily to lower revenue for research models services and the Cell Solutions business, as well as lower sales for non-human primates (NHPs) in China. The decline was partially offset by higher sales of small research models, principally driven by higher pricing.
In the fourth quarter of 2024, the RMS segment’s GAAP operating margin decreased to 6.7% from 18.9% in the fourth quarter of 2023. On a non-GAAP basis, the operating margin decreased to 22.8% from 23.1%. The GAAP and non-GAAP operating margin declines were primarily driven by research models services and NHP sales, partially offset by higher pricing for small research models and from cost savings associated with restructuring initiatives. On a GAAP basis, the lower operating margin also reflects higher costs associated with the Company’s restructuring initiatives, including severance and site consolidation costs, as well as higher amortization expense related to the Noveprim acquisition.
Discovery and Safety Assessment (DSA)

Revenue for the DSA segment was $603.3 million in the fourth quarter of 2024, a decrease of 3.6% from $625.8 million in the fourth quarter of 2023. The divestiture of a small Safety Assessment site reduced reported revenue by 0.2% and the impact of foreign currency translation increased DSA revenue by 0.1%. Organic revenue decreased by 3.5%, driven primarily by lower sales volume, as well as slightly lower pricing.

In the fourth quarter of 2024, the DSA segment’s GAAP operating margin decreased to 10.4% from 20.2% in the fourth quarter of 2023. On a non-GAAP basis, the operating margin decreased to 24.7% from 26.0% in the fourth quarter of 2023. The GAAP and non-GAAP operating margin declines were primarily driven by lower revenue, partially offset by cost savings associated with restructuring initiatives. On a GAAP basis, the lower operating margin also reflects an NHP inventory write down, as well as higher acquisition-related adjustments associated with Noveprim.

Manufacturing Solutions (Manufacturing)

Revenue for the Manufacturing segment was $194.9 million in the fourth quarter of 2024, an increase of 1.6% from $191.9 million in the fourth quarter of 2023. The impact of foreign currency translation reduced Manufacturing revenue by 0.5%. Organic revenue increased 2.1%, primarily driven by the Microbial Solutions business. This was partially offset by lower revenue in the CDMO business.

Primarily as a result of the non-cash goodwill impairment, the Manufacturing segment’s GAAP operating margin decreased to (93.6)% from 18.5% in the fourth quarter of 2023. On a non-GAAP basis, the operating margin increased to 28.7% from 25.4% in the fourth quarter of 2023 driven primarily by improved operating leverage from higher revenue in the Microbial Solutions business, as well as the benefit of cost savings associated with restructuring initiatives.

Full-Year Results
For 2024, revenue decreased by 1.9% to $4.05 billion from $4.13 billion in 2023. Revenue declined by 2.8% on an organic basis.
The GAAP operating margin decreased to 5.6% from 14.9% in 2023, and on a non-GAAP basis, the operating margin decreased to 19.9% from 20.3%.
On a GAAP basis, net income available to common shareholders was $10.3 million in 2024, a decrease of 97.8% from $474.6 million in 2023. Diluted earnings per share on a GAAP basis in 2024 were $0.20, a decrease of 97.8% from $9.22 in 2023. The GAAP decreases were primarily driven by the non-cash goodwill impairment of $215.0 million, or $4.16 per share, as well as the loss on certain venture capital and other strategic investments of $0.15 per share in 2024. This compares to a gain of $1.87 per share on certain venture capital and other strategic investments in 2023.
On a non-GAAP basis, net income was $532.9 million in 2024, a decrease of 2.9% from $548.9 million in 2023. Diluted earnings per share on a non-GAAP basis in 2024 were $10.32, a decrease of 3.3% from $10.67 in 2023.
Research Models and Services (RMS)
For 2024, RMS revenue was $829.4 million, an increase of 4.7% from $792.3 million in 2023. Revenue declined by 0.1% on an organic basis.

On a GAAP basis, the RMS segment operating margin decreased to 13.8% in 2024 from 19.5% in 2023. On a non-GAAP basis, the operating margin increased to 23.7% in 2024 from 23.0% in 2023.

Discovery and Safety Assessment (DSA)
For 2024, DSA revenue was $2.45 billion, a decrease of 6.3% from $2.62 billion in 2023. Revenue declined by 6.2% on an organic basis.

On a GAAP basis, the DSA segment operating margin decreased to 18.1% in 2024 from 23.2% in 2023. On a non-GAAP basis, the operating margin decreased to 25.7% in 2024 from 27.5% in 2023.

Manufacturing Solutions (Manufacturing)
For 2024, Manufacturing revenue was $769.3 million, an increase of 6.6% from $721.4 million in 2023. Organic revenue growth was 6.8%.

On a GAAP basis, the Manufacturing segment operating margin decreased to (9.3)% in 2024 from 12.2% in 2023. The GAAP operating margin was impacted by the non-cash goodwill impairment. On a non-GAAP basis, the operating margin increased to 27.4% in 2024 from 21.8% in 2023.

Provides 2025 Guidance
The Company is providing financial guidance for 2025. The 2025 revenue outlook assumes relatively stable biopharmaceutical demand trends compared to those experienced during the second half of 2024, including continued budgetary constraints from global biopharmaceutical clients and stable to slightly improved demand from small and mid-sized biotechnology clients. In addition, we expect that DSA pricing will be a headwind to revenue growth throughout 2025, and that lower commercial revenue in the CDMO business will impact the Manufacturing segment’s growth rate. Earnings per share in 2025 will principally be affected by the lower revenue, partially offset by the benefit of cost savings associated with the Company’s restructuring initiatives. The Company plans to repurchase approximately $350 million in common stock in 2025.
The Company’s 2025 guidance for revenue and earnings per share is as follows:

2025 GUIDANCE
Revenue growth/(decrease), reported
(7.0)% – (4.5)%
Impact of divestitures/(acquisitions), net
N/M
(Favorable)/unfavorable impact of foreign exchange
1.0% – 1.5%
Revenue growth/(decrease), organic (1)
(5.5)% – (3.5)%
GAAP EPS estimate
$4.30 – $4.80
Acquisition-related amortization and other acquisition- and integration-related costs (2)
~$3.50
Costs associated with restructuring actions (3)
~$1.00
Other items (4)
~$0.30
Non-GAAP EPS estimate
$9.10 – $9.60

Footnotes to Guidance Table:
(1) Organic revenue growth is defined as reported revenue growth adjusted for completed acquisitions and divestitures, as well as foreign currency translation.
(2) These adjustments include amortization related to intangible assets, as well as the purchase accounting step-up on inventory and certain long-term biological assets. In addition, these adjustments include some costs related to the evaluation and integration of acquisitions and divestitures.
(3) These adjustments primarily include site consolidation (including site transition costs), severance, impairment, and other costs related to the Company’s restructuring actions.
(4) These items primarily relate to certain third-party legal costs related to investigations by the U.S. government into the NHP supply chain related to our Safety Assessment business.

Webcast
Charles River has scheduled a live webcast on Wednesday, February 19th, at 8:30 a.m. ET to discuss matters relating to this press release. To participate, please go to ir.criver.com and select the webcast link. You can also find the associated slide presentation and reconciliations of GAAP financial measures to non-GAAP financial measures on the website.