On April 29, 2025 Rakovina Therapeutics Inc. (TSX-V: RKV) (FSE: 7JO), a biopharmaceutical company advancing next-generation cancer therapies through artificial intelligence (AI)-powered drug discovery, reported the presentation of new preclinical data from two of its lead programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Rakovina Therapeutics, APR 29, 2025, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-showcases-preclinical-results-of-novel-ai-discovered-cancer-therapies-at-aacr-2025 [SID1234652322]).

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The first presentation highlighted Rakovina’s PARP1-selective inhibitor program. Using the proprietary Deep Docking and generative platforms , Rakovina previously screened more than four billion potential drug-like molecules to identify a shortlist of top candidates. These compounds were synthesized and evaluated in Rakovina’s laboratory facilities at the University of British Columbia.

Data presented at AACR (Free AACR Whitepaper) demonstrated a new class of PARP1 inhibitors with significantly improved metabolic stability, including the lowest in vitro clearance rates and the longest half-life compared to other candidates currently in development. Early animal studies revealed strong plasma exposure and a promising pharmacokinetic profile suggestive of central nervous system (CNS) penetration — a potentially significant advantage in treating brain-involved malignancies.

The second presentation showcased progress from Rakovina’s ATR-specific inhibitor program, developed in partnership with Variational AI. Researchers identified a focused set of lead candidates predicted to be highly potent and selective against ATR, a key DNA damage response target. These candidates are also designed with the potential to cross the blood-brain barrier, an important feature for addressing cancers affecting the CNS. The top candidates are currently being synthesized for laboratory validation.

"Our ability to screen billions of molecules and advance top candidates to in vitro and in vivo validation within months — rather than years — exemplifies the transformative power of AI in drug discovery," said Jeffrey Bacha, Executive Chairman of Rakovina Therapeutics. "This acceleration gives us the opportunity to significantly reduce the time and cost required to bring new life-saving cancer treatments to patients."

The results presented at AACR (Free AACR Whitepaper) reinforce the robustness of Rakovina’s AI-enabled discovery platform. Moving forward, Rakovina will leverage these findings to further refine and train its AI models, with the goal of advancing best-in-class lead candidates for both the PARP1 and ATR programs into clinical development. The Company intends to collaborate with pharmaceutical partners to accelerate the path to the clinic and deliver novel therapies to patients in need.

On April 29, 2025 Bayer reported new post-hoc analyses from the investigational Phase III ARANOTE trial showed that patients receiving NUBEQA (darolutamide) plus androgen deprivation therapy (ADT) were more likely to experience an ultra-low (<0.02 ng/mL) prostate specific androgen (PSA) response (42.6%) at any time versus patients receiving placebo plus ADT (7.8%), with ultra-low response rates in the NUBEQA group being higher than in the placebo group regardless of baseline PSA (Press release, Bayer, APR 29, 2025, View Source [SID1234652339]). The post-hoc analyses from the pivotal ARANOTE trial also showed that in patients receiving NUBEQA plus ADT, achieving ultra-low PSA response correlated with prolonged radiographic progression-free survival (rPFS) time (HR 0.09; 95% CI: 0.05–0.16), time to metastatic castration-resistant prostate cancer (mCRPC) (HR 0.07; 95% CI: 0.04–0.11) and time to PSA progression (HR 0.02; 95% CI: 0.01–0.05).1

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The safety profile of NUBEQA was independent of PSA response, with lower treatment discontinuation rates due to treatment emergent adverse events (TEAEs) in patients receiving NUBEQA plus ADT versus placebo.1

The results were presented today at the 2025 American Urological Association (AUA) Annual Meeting in Las Vegas, Nevada. NUBEQA is indicated in the U.S. for the treatment of adult patients with mHSPC in combination with docetaxel and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC).2

Prostate cancer is the second most common cancer in men.3 Only 30% of those diagnosed with mHSPC will survive five years or more after diagnosis.4 Most people with mHSPC eventually progress to mCRPC, a condition with limited long-term survival.5,6

"The subgroup analyses of the ARANOTE trial contribute to the valuable insights of the management of metastatic hormone-sensitive prostate cancer and equip physicians with additional data to help inform treatment options," said Dr. Neal Shore, Medical Director, Carolina Urologic Research Center and Urologist at AUC Urology Specialists, Myrtle Beach, South Carolina.

"At Bayer, we are committed to redefining prostate cancer care and enhancing patient outcomes at various stages of the disease. The growing evidence supporting NUBEQA reinforces its potential to meet the needs of men with prostate cancer," said Christine Roth, Global Head of Product Strategy and Commercialization at Bayer’s Pharmaceuticals Division. "These data add to the meaningful insights from the ARANOTE trial which can be leveraged by physicians to inform clinical decisions, helping them to identify the right treatment options for their patients living with prostate cancer."

About the ARANOTE Trial7
The ARANOTE trial (NCT04736199) is a Phase III, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of NUBEQA in combination with standard ADT in patients with mHSPC. A total of 669 patients were randomized 2:1 to receive either 600 mg of NUBEQA (n=446) or placebo (n=223) twice daily in addition to ADT.

The primary endpoint of the ARANOTE trial was rPFS, which was statistically significant for the NUBEQA arm vs placebo arm (HR: 0.54; 95% CI: 0.41-0.71; P < 0.0001), measured as time from randomization to date of first documented radiological disease progression or death due to any cause, whichever occurs first. Secondary endpoints include overall survival (OS; time to death from any cause), time to first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to PSA progression, PSA undetectable rates, time to pain progression, and safety assessments.

Initial results from pivotal Phase III ARANOTE trial (n=669), published in The Journal of Clinical Oncology and presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, demonstrated a statistically significant improvement in rPFS with a 46% reduction in the risk of radiologic progression or death (HR 0.54; 95% CI: 0.41-0.71; P<0.0001) compared to placebo plus ADT.8

About NUBEQA (darolutamide)2
NUBEQA (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.

NUBEQA is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with:

Non-metastatic castration-resistant prostate cancer (nmCRPC)
Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
IMPORTANT SAFETY INFORMATION

Warnings & Precautions
Ischemic Heart Disease – In a study of patients with nmCRPC (ARAMIS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA versus 2.5% receiving placebo, including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA vs. 0.2% receiving placebo. In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel vs. 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel vs. 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease.

Seizure – In ARAMIS, Grade 1-2 seizure occurred in 0.2% of patients receiving NUBEQA vs. 0.2% receiving placebo. Seizure occurred 261 and 456 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.6% of patients receiving NUBEQA with docetaxel, including one Grade 3 event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred 38 to 340 days after initiation of NUBEQA. It is unknown whether antiepileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment.

Embryo-Fetal Toxicity – Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions
In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA vs. 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA vs. 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common adverse reactions (>2% with a ≥2% increase over placebo), including laboratory test abnormalities, were increased AST, decreased neutrophil count, fatigue, increased bilirubin, pain in extremity and rash. Clinically relevant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease and heart failure.

In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs. 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), decreased neutrophil count (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs. 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, rash, decreased appetite, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia. Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures, ischemic heart disease, seizures, and drug-induced liver injury.

Drug Interactions
Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

About Metastatic Hormone-Sensitive Prostate Cancer
Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death in men worldwide.3.9 In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, including almost 300,000 cases in the U.S., and about 375,000 died from the disease worldwide.10,11

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 10% of men will already present with mHSPC when first diagnosed.12,13,14 Men with mHSPC will start their treatment with hormone therapy, such as ADT, androgen receptor inhibitor (ARi) plus ADT or a combination of the chemotherapy docetaxel and ADT. Despite this treatment, most men with mHSPC will eventually progress to mCRPC, a condition with limited survival.

On April 29, 2025 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of its lead immune-activating antibody therapeutic, reported positive results from its Phase 1/2 dose escalation and cohort expansion study of its investigational candidate AU-007 (Press release, Aulos Bioscience, APR 29, 2025, View Source [SID1234652302]). The data were shared in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois.

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The interim Phase 2 data demonstrate clear evidence of durable partial and complete tumor response in multiple cancer types, including patients with melanoma whose tumors had progressed through prior checkpoint inhibitors and who received a combination of AU-007 and low-dose, subcutaneous aldesleukin. Durable tumor shrinkages were also observed in patients with checkpoint inhibitor-resistant or progressed renal cell carcinoma (RCC) who received the same AU-007 and aldesleukin regimen. Additionally, AU-007 and low-dose, subcutaneous aldesleukin continues to demonstrate a unique pharmacodynamic (PD) profile in the interleukin-2 (IL-2) class, with regulatory T cells (Tregs) decreasing and CD8 effector T cells expanding at all AU-007 dose levels.

"We are very pleased with the clinical activity observed with AU-007 and low-dose, subcutaneous aldesleukin without a checkpoint inhibitor, as it accentuates our confidence in AU-007 as a potential best-in-class therapeutic for multiple cancers," said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. "Deep and durable tumor shrinkages, including complete responses, are occurring in patients who were refractory to treatment and had achieved no responses from highly potent prior immuno-oncology regimens. Importantly, the results reinforce the previously reported observation that the CD8 effector T cell expansion and Treg reduction correlates with clinical efficacy. This key driver of Treg reduction coupled with CD8 effector T cell expansion and enhancement of the CD8/Treg ratio differentiates AU-007 from other IL-2 therapeutic programs. Today’s data support further evaluation of AU-007 and low-dose, subcutaneous aldesleukin as a second-line treatment for melanoma, where limited treatment options exist. Our new Phase 2 cohort augmenting this regimen with anti-PD-1 nivolumab is now enrolling patients and we look forward to presenting preliminary data later this year."

Key findings from interim results of the Phase 1/2 dose escalation and cohort expansion study of AU-007, with data available on 95 patients as of the data cutoff date of March 20, 2025, are as follows:

Continued tolerable and manageable safety profile was observed with AU-007 as a monotherapy and in combination with low-dose, subcutaneous aldesleukin at all doses evaluated in Phase 1 dose escalation.

No dose-limiting toxicity occurred throughout Phase 1 dose escalation.
Most drug-related adverse events were mild and transient Grade 1 or 2 events.
The most common treatment-related adverse events in patients who received AU-007 and low-dose, subcutaneous aldesleukin were Grade 1 or 2 fatigue (21%), pyrexia (21%), chills (19%) and infusion-related reaction (15%).
The incidence of Grade 3 or 4 treatment-related adverse events in patients who received AU-007 and low-dose, subcutaneous aldesleukin was cytokine release syndrome (1%), lymphopenia (8%) and anemia (3%). All events were transient and resolved, and there were no Grade 5 treatment-related adverse events.
Durable objective responses were observed in patients with multiple tumor types enrolled in the Phase 1 dose escalation and Phase 2 cohorts.

One patient with metastatic bladder cancer that progressed on an anti-PD-L1 treatment was treated with AU-007 every two weeks (Q2W) and one loading dose of low-dose, subcutaneous aldesleukin, has an ongoing metabolic complete response and continues on treatment for two years.
One patient with metastatic nasopharyngeal head and neck cancer that progressed on five prior systemic therapies received AU-007 and low-dose, subcutaneous aldesleukin Q2W. This patient experienced an unconfirmed complete response after 20 months and continues on treatment.
Three patients with melanoma refractory to either prior anti-CTLA-4 and anti-PD-1 or anti-PD-1 and anti-LAG-3 therapy were treated with AU-007 Q2W and one loading dose of low-dose, subcutaneous aldesleukin, and experienced deep and durable tumor shrinkages of 100% (complete response in all target lesions, continues on study for 13+ months), 58% (continues on study for 10+ months) and 48% (on study for 13 months).
One patient in dose escalation with acral melanoma that progressed rapidly on prior anti-PD-1 therapy received AU-007 and one loading dose of low-dose, subcutaneous aldesleukin. This patient remained on AU-007 therapy for 11 months with disease control.
The regimen of AU-007 and low-dose, subcutaneous aldesleukin exhibits distinct pharmacodynamic effects in the class and continues to drive durable decreases in Tregs, increases in CD8 T cells, and corresponding increases in CD8/Treg ratios.

A decrease in Tregs appears to be a critical determinant of observed efficacy, with Tregs decreasing in the periphery in the presence of AU-007 at all dose levels.
This finding supports AU-007’s overall mechanism of action to control and redirect endogenously produced IL-2 and exogenously administered IL-2 to reduce the Treg population and increase circulating CD8 effector T cell populations. Treg cells are highly immunosuppressive cells that can blunt the immune response to tumors and reduce the durability of responses and progression-free survival.
The Phase 2 expansion cohorts evaluating AU-007 and a single loading dose of low-dose, subcutaneous aldesleukin continue to enroll patients with advanced cutaneous melanoma who have failed prior checkpoint inhibitor therapy as well as patients with PD-L1+ non-small cell lung cancer (NSCLC) who have failed prior checkpoint inhibitor therapy.

An additional Phase 2 cohort is evaluating AU-007 and low-dose, subcutaneous aldesleukin combined with avelumab (checkpoint inhibitor with ADCC effector function; anti-PD-L1) in PD-L1+ NSCLC in patients who have failed prior checkpoint inhibitor therapy. As announced earlier this month, a new Phase 2 cohort evaluating AU-007 and a single subcutaneous loading dose of low-dose aldesleukin combined with nivolumab (checkpoint inhibitor; anti-PD-1) as a second-line treatment for cutaneous melanoma is enrolling patients who have not received a prior BRAF/MEK inhibitor. Aulos anticipates presenting preliminary clinical data from these two Phase 2 expansion cohorts in the second half of 2025.

The poster, "AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin, in advanced solid tumors: Phase 2 update," (Abstract CT178) is accessible to meeting registrants as an electronic poster on the AACR (Free AACR Whitepaper) 2025 virtual meeting platform. It is also available on the Aulos Bioscience website in the Abstracts and Publications section.

To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.

About AU-007
AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

On April 29, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the first quarter of 2025 and provided a business update (Press release, Regeneron, APR 29, 2025, View Source [SID1234652324]).

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"Regeneron has one of the most exciting pipelines in the industry, with unmatched diversity, scientific distinction, and potential to help millions of patients," said Leonard S. Schleifer, M.D., Ph.D., Board co-Chair, President and Chief Executive Officer of Regeneron. "We are laser focused on fulfilling the promise of this pipeline by advancing our clinical programs, and expect several important data readouts this year. We are also working to ensure our four blockbuster medicines reach even more patients who could benefit, with year-to-date progress including regulatory approvals for Dupixent in CSU in the U.S. and COPD in Japan."

Financial Highlights

($ in millions, except per share data) Q1 2025 Q1 2024 % Change
Total revenues $ 3,029 $ 3,145 (4 %)
GAAP net income $ 809 $ 722 12 %
GAAP net income per share – diluted $ 7.27 $ 6.27 16 %
Non-GAAP net income(a) $ 928 $ 1,116 (17 %)
Non-GAAP net income per share – diluted(a) $ 8.22 $ 9.55 (14 %)

"We have made meaningful progress across our pipeline so far in 2025, including four regulatory approvals, nine regulatory submissions, and are poised to report pivotal or proof-of-concept data across programs in immunology, oncology, hematology, internal medicine, and rare diseases later this year," said Christopher Fenimore, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "We continue to deploy capital with the goal of maximizing long-term shareholder value, with a focus on internal investment in our research, development, and commercial capabilities, along with returning capital directly to our shareholders through opportunistic share repurchases and our dividend program, which we initiated earlier this year."

Business Highlights

Key Pipeline Progress
Regeneron has approximately 45 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

Dupixent (dupilumab)

In April 2025, the U.S. Food and Drug Administration (FDA) approved Dupixent for the treatment of adults and adolescents aged 12 years and older with CSU who remain symptomatic despite antihistamine treatment.
In March 2025, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved Dupixent for the treatment of patients with COPD.
The Company and Sanofi presented positive results from the pivotal Phase 2/3 trial in adults with moderate-to-severe bullous pemphigoid at the 2025 American Academy of Dermatology (AAD) Annual Meeting. In February 2025, the FDA accepted for priority review the supplemental Biologics License Application (sBLA) for Dupixent in bullous pemphigoid, with a target action date of June 20, 2025. A regulatory application has also been submitted in the European Union (EU).

EYLEA HD (aflibercept) 8 mg

In April 2025, the FDA accepted for priority review an sBLA for both the treatment of macular edema following RVO, and broadening the dosing schedule to include every 4-week (monthly) dosing across approved indications. The FDA target action date is August 19, 2025, following the use of a priority review voucher.
The FDA issued a Complete Response Letter (CRL) for the EYLEA HD pre-filled syringe on April 23, 2025. The Company held several teleconferences with the FDA to better understand the contents of the CRL, and believes the key outstanding issue relates to a question posed by the FDA to a third-party component supplier. This component supplier has expeditiously responded to FDA requests for information. The CRL did not identify any issues with the safety or efficacy of EYLEA HD, the usability of the device, proposed labelling, or pre-approval inspection findings.
In April 2025, the FDA issued a CRL regarding the sBLA for the addition of extended dosing intervals. The FDA indicated that the submitted data did not support extended dosing intervals greater than every 16 weeks. The Company is evaluating the FDA’s decision.
The Company presented positive results from the Phase 3 QUASAR trial for the treatment of patients with macular edema following RVO, including those with central, branch, and hemiretinal vein occlusions, at the Angiogenesis, Exudation, and Degeneration (Angiogenesis) 2025 annual meeting.
The Company announced positive three-year (156-week) results from an extension study of the Phase 3 PULSAR trial in patients with wet age-related macular degeneration (wAMD). Similar to the three-year results for the pivotal PHOTON trial in diabetic macular edema (DME), the longer-term wAMD data demonstrated the vast majority of patients who entered the extension study sustained the visual gains and anatomic improvements achieved by the end of the second year, while also achieving substantially longer treatment intervals. The results were presented at the Angiogenesis 2025 annual meeting.

Oncology Programs

The Company submitted an sBLA to the FDA and a regulatory application in the EU for Libtayo (cemiplimab) in adjuvant CSCC based upon data from a Phase 3 trial which demonstrated that adjuvant treatment with Libtayo was the first and only immunotherapy that led to a statistically significant and clinically meaningful improvement in the primary endpoint of disease-free survival (DFS) in patients with high-risk CSCC after surgery.
The FDA accepted for review the resubmission of the BLA for odronextamab, a bispecific antibody targeting CD20 and CD3, in relapsed/refractory (R/R) follicular lymphoma, with a target action date of July 30, 2025.
The FDA accepted for review the resubmission of the BLA for linvoseltamab, a bispecific antibody targeting BCMA and CD3, in R/R multiple myeloma, with a target action date of July 10, 2025.
The European Commission (EC) granted conditional marketing approval of Lynozyfic (linvoseltamab) to treat adults with R/R multiple myeloma. The indication is specific to those who have received at least three prior therapies including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy.
Enrollment was completed in a Phase 3 confirmatory trial (LINKER-MM3) for linvoseltamab in R/R multiple myeloma.

Other Programs

The Company presented updated data from the Phase 1/2 trial of DB-OTO, an AAV-based gene therapy, in children with profound genetic hearing loss due to variants of the otoferlin (OTOF) gene at the Association for Research in Otolaryngology’s (ARO) 48th Annual MidWinter Meeting. The data showed that 11 out of 12 children treated demonstrated a notable response, with improved hearing at various decibel hearing levels. This included updated results from the first child dosed, who received treatment at 10 months of age and at 48 weeks post-treatment showed continued near-normal levels of hearing, as well as formal speech perception improvements between 48- and 72-weeks post-treatment.
A Phase 3 study for itepekimab, an antibody to IL-33, in chronic rhinosinusitis with nasal polyposis (CRSwNP) was initiated.
A Phase 2 study for REGN5381, an agonist antibody to NPR1, in uncontrolled hypertension was initiated.
A Phase 2 study for REGN7544, an antagonist antibody to NPR1, in sepsis-induced hypotension was initiated.
The FDA granted Orphan Drug designation for mibavademab, an agonist antibody to leptin receptor (LEPR), in generalized lipodystrophy; a Phase 3 study is ongoing.

Corporate Updates

The Company reached resolution of its patent infringement litigation related to Biocon’s EYLEA (aflibercept) Injection 2 mg biosimilar product. The settlement precludes Biocon from launching its biosimilar product in the United States until the second half of 2026. All intellectual property-related litigation with Biocon in the United States has been dismissed.
The Company announced a 10-year agreement with FUJIFILM Diosynth Biotechnologies (Fujifilm) to manufacture and supply Regeneron’s commercial bulk drug product at Fujifilm’s North Carolina campus. The agreement is anticipated to nearly double the Company’s large-scale manufacturing capacity in the United States.
First Quarter 2025 Financial Results

Revenues

($ in millions) Q1 2025 Q1 2024 % Change
Net product sales:
EYLEA HD – U.S. $ 307 $ 200 54 %
EYLEA – U.S. 736 1,202 (39 %)
Total EYLEA HD and EYLEA – U.S. 1,043 1,402 (26 %)
Libtayo – U.S. 192 159 21 %
Libtayo – ROW** 93 105 (11 %)
Total Libtayo – Global 285 264 8 %
Praluent – U.S. 57 70 (19 %)
Evkeeza – U.S. 31 24 29 %
Inmazeb – ROW — 1 (100 %)
Total net product sales 1,416 1,761 (20 %)

Collaboration revenue:
Sanofi 1,183 910 30 %
Bayer 344 356 (3 %)
Other 4 1 *
Other revenue 82 117 (30 %)
Total revenues $ 3,029 $ 3,145 (4 %)

* Percentage not meaningful
** Rest of world (ROW)

Net product sales of EYLEA HD increased in the first quarter of 2025, compared to the first quarter of 2024, primarily due to higher sales volumes.

Net product sales of EYLEA in the first quarter of 2025, compared to the first quarter of 2024, were negatively impacted by (i) lower volume as a result of continued competitive pressures (as described below), loss in market share to compounded bevacizumab due to patient affordability constraints, and the continued transition of patients to EYLEA HD, and (ii) a lower net selling price.

In addition, total EYLEA and EYLEA HD net product sales were negatively impacted by lower wholesaler inventory levels at the end of the first quarter of 2025 compared to the end of the fourth quarter of 2024. Total EYLEA and EYLEA HD net product sales decreased 30% on a sequential basis; however, physician unit demand decreased sequentially by 11%.

EYLEA net product sales have been, and are likely to continue to be, negatively impacted by increased competition from other anti-VEGF products, including biosimilars, as well as the transition of patients from EYLEA to EYLEA HD. In addition, if independent not-for-profit patient assistance funds that provide copay assistance are unable to support eligible patients, this will likely have a continued negative impact on patient affordability resulting in lower utilization of higher-cost anti-VEGF agents.

Sanofi collaboration revenue increased in the first quarter of 2025, compared to the first quarter of 2024, due to an increase in the Company’s share of profits from the commercialization of antibodies, which were $1.018 billion and $804 million in the first quarter of 2025 and 2024, respectively. The change in the Company’s share of profits from commercialization of antibodies was driven by higher profits associated with an increase in Dupixent sales.

Refer to Table 4 for a summary of collaboration revenue.

Operating Expenses

GAAP %
Change
Non-GAAP(a) %
Change

($ in millions) Q1 2025 Q1 2024 Q1 2025 Q1 2024
Research and development (R&D) $ 1,327 $ 1,248 6 % $ 1,186 $ 1,122 6 %
Acquired in-process research and development (IPR&D) $ 12 $ 7 71 % * * n/a
Selling, general, and administrative (SG&A) $ 633 $ 689 (8 %) $ 537 $ 584 (8 %)
Cost of goods sold (COGS) $ 266 $ 240 11 % $ 217 $ 196 11 %
Gross margin on net product sales(c) 81% 86% 85% 89%
Cost of collaboration and contract manufacturing (COCM) $ 199 $ 193 3 % * * n/a
Other operating expense (income), net $ — $ 15 (100 %) * $ — — %

* GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been recorded

GAAP and non-GAAP R&D expenses increased in the first quarter of 2025, compared to the first quarter of 2024, driven by the advancement of the Company’s clinical pipeline and higher personnel-related costs.
GAAP and non-GAAP gross margin on net product sales was adversely impacted by higher inventory write-offs and reserves in the first quarter of 2025 compared to the first quarter of 2024.
Other Financial Information

GAAP other income (expense), net included the recognition of net unrealized gains on equity securities of $140 million in the first quarter of 2025, compared to $196 million of net unrealized losses in the first quarter of 2024.

In the first quarter of 2025, the Company’s GAAP effective tax rate (ETR) was 10.6%, compared to (3.0%) in the first quarter of 2024. The GAAP ETR increased in the first quarter of 2025, compared to the first quarter of 2024, due to lower tax benefits from less stock option exercises. In the first quarter of 2025, the non-GAAP ETR was 11.6%, compared to 6.1% in the first quarter of 2024.

A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

Capital Allocation

In February 2025, the Company’s board of directors authorized a new share repurchase program to repurchase up to an additional $3.0 billion of the Company’s common stock. During the first quarter of 2025, the Company repurchased shares of its common stock and recorded the cost of the shares, or $1.052 billion, as Treasury Stock. As of March 31, 2025, an aggregate of $3.874 billion remained available for share repurchases under the Company’s share repurchase programs.

In April 2025, the Company’s board of directors declared a cash dividend of $0.88 per share on the Company’s common stock and Class A stock, payable on June 6, 2025 to shareholders of record as of May 20, 2025.

On April 29, 2025 Pilatus Biosciences, a biotechnology company developing immunometabolic therapies for cancer, reported a preclinical publication in Cancer Discovery detailing the mechanism and therapeutic potential of its lead candidate, PLT012 (Press release, Pilatus Biosciences, APR 29, 2025, View Source [SID1234652340]).

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The paper, titled: "PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Anti-Tumor Immunity Against Liver Cancer and Liver Metastasis," establishes PLT012 as the first humanized antibody to target CD36, a lipid scavenger receptor implicated in immune dysfunction in metabolically hostile tumor microenvironments and highlights its efficacy in restoring anti-tumor immunity in hepatocellular carcinoma (HCC) and colorectal liver metastases.

CD36 is upregulated in immune cells exposed to lipid-rich, inflammatory environments and has emerged as a key driver of immune suppression in solid tumors. By blocking CD36-mediated lipid uptake, PLT012 reduces intratumoral Tregs and pro-tumor macrophages, while enhancing CD8+ T cell infiltration, survival, and cytotoxicity.

"Liver cancer presents a unique opportunity to improve patient outcomes by addressing the underlying immunometabolic suppression that can limit the effectiveness of current checkpoint inhibitors," said Yi-Ru Yu, Ph.D., Lead Scientist of Pilatus Biosciences and co-first author of the study. "Our data show that PLT012, our lead CD36-targeting immunometabolic therapy, restores immune function at its metabolic core to reprogram the tumor environment to enable effective and durable anti-tumor responses."

Key Findings from the Cancer Discovery Study:

PLT012 monotherapy drives tumor regression in both immune-inflamed and immune-excluded HCC models, including β-catenin–driven tumors resistant to checkpoint blockade.
In combination with anti-PD-L1 and anti-VEGF therapies, PLT012 significantly improves tumor control and increases complete response rates.
In colorectal cancer models with liver metastases, PLT012 restores responsiveness to PD-1 blockade and reprograms macrophage phenotypes.
Ex vivo validation in human HCC samples showed increased CD8+ T cell activity in 45% of patient samples and decreased Tregs in 82% of samples treated with PLT012.
Toxicology studies in non-human primates confirmed a favorable safety profile, with no adverse effects observed at doses up to 200 mg/kg.
"This work validates CD36 as a tractable target in immuno-oncology and positions PLT012 as a first-in-class therapeutic with broad potential across solid tumors characterized by metabolic immune suppression," said Raven Lin, CEO & Founder, Pilatus Biosciences. "These important milestones highlight PLT012’s potential to transform treatment for patients with advanced solid tumors."

"The ability of PLT012 to reprogram the tumor microenvironment by overcoming metabolic immune suppression marks a major advancement for the field of immuno-oncology," said Ping-Chih Ho, Ph.D., Co-Founder and Chair of the Scientific Advisory Board at Pilatus Biosciences, who presented the data as an oral presentation at AACR (Free AACR Whitepaper) 2025. "Our findings validate CD36 as a novel immunometabolic target and demonstrate the broad potential of PLT012 to restore effective anti-tumor immunity across solid tumors. I look forward to seeing Pilatus bring this important new therapeutic approach into clinical development."

PLT012 has received FDA Orphan Drug Designation for the treatment of HCC and intrahepatic bile duct cancer, reinforcing its potential to address rare, aggressive liver malignancies with limited treatment options. Pilatus is advancing PLT012 through IND-enabling studies, with plans to file an IND by end of 2025 to initiate clinical development next year.

About PLT012

PLT012 is a humanized monoclonal antibody designed to selectively block CD36-mediated lipid uptake, a key mechanism driving immunosuppression and immune exclusion within the tumor microenvironment. PLT012 simultaneously reduces Tregs and pro-tumor macrophages while enhancing anti-tumor activities of intratumoral NK cell and cytotoxic CD8+ T cell. The antibody has demonstrated potent monotherapy and combination activity in preclinical models of HCC, liver metastases, and high-fat-diet–induced tumor progression, with a favorable safety profile across species.