On April 29, 2025 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a life sciences company developing innovative targeted oncology therapies and commercializing RenovoCath, a novel, FDA-cleared drug-delivery device, reported that Johns Hopkins Medicine is now initiated to enroll patients with locally advanced pancreatic cancer (LAPC) in RenovoRx’s ongoing Phase III TIGeR-PaC clinical trial (Press release, Renovorx, APR 29, 2025, View Source [SID1234652338]). Johns Hopkins Medicine becomes the newest addition to a distinguished network of clinical cancer sites across the United States participating in this important trial.

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The initiation of patient enrollment at Johns Hopkins Medicine will be at their Sibley Memorial Hospital campus and marks the most recent site to support RenovoRx’s path to completing patient enrollment for the trial. RenovoRx is expecting to achieve full enrollment in the TIGeR-PaC trial during 2025.

In addition, RenovoRx announced that John Hopkins Medicine’s Valerie Lee, MD, Medical Oncologist, has been appointed as TIGeR-PaC Principal Investigator (PI) at Johns Hopkins Medicine. Michael J. Pishvaian, MD, PhD, Director of Gastrointestinal, Developmental Therapeutics and Clinical Research Programs at John Hopkins Medicine, currently serves as Trial Chairman for the entire TIGeR-PaC trial.

The TIGeR-PaC trial is evaluating RenovoRx’s lead drug-device combination product candidate, intra-arterial delivery of gemcitabine (IAG) via the FDA-cleared RenovoCath device, which uses RenovoRx’s proprietary Trans-Arterial Micro-Perfusion (TAMP) therapy platform for the treatment of LAPC. This drug-device combination product candidate is currently under FDA investigation and has not been approved for commercial sale. The trial is comparing treatment with IAG in LAPC to the current standard-of-care (systemic intravenous chemotherapy).

"We are pleased that Johns Hopkins Medicine has been initiated to begin enrollment in our ongoing Phase III TIGeR-PaC clinical trial," said Leesa Gentry, Chief Clinical Officer of RenovoRx. "The addition of this prestigious cancer center further strengthens our trial. The philosophy of Johns Hopkins Medicine’s leading researchers and clinicians aligns strongly with our vision of providing specialized medicine that translates into personalized care for improved patient outcomes. Dr. Michael Pishvaian, who has served as our TIGeR-PaC Trial Chair since the trial’s inception, will continue to provide deep understanding of the pancreatic cancer landscape. With the addition of Johns Hopkins Medicine as a clinical trial site, Dr. Valerie Lee will join the trial serving as Principal Investigator. This new clinical site will help drive enrollment of the TIGeR-PaC trial to completion as they treat a large number of patients diagnosed with pancreatic cancer. We are proud to partner with Johns Hopkins Medicine as well as our other TIGeR-PaC clinical sites as they strive to provide the best in care for patients diagnosed with difficult-to-treat tumors like pancreatic cancer."

At Johns Hopkins Medicine, Dr. Lee’s expertise includes management of gastrointestinal malignancies, including gastric, colon, and pancreatobiliary cancers. She also oversees multiple early-phase clinical trials, with her research being published in numerous peer-reviewed journals.

Johns Hopkins Medicine’s Sibley Memorial Hospital campus ranks among the top hospitals in the Washington, D.C., metropolitan area, delivering comprehensive healthcare services to local communities. The hospital provides an extensive array of care, including medical, surgical, intensive care, obstetric, oncology, and orthopedic services, alongside numerous inpatient and outpatient offerings.

The current protocol and statistical analysis plan for the TIGeR-PaC trial requires 114 randomized patients, with 86 events (i.e., patient deaths) necessary to complete the final analysis. As of March 28, 2025, 90 patients have been randomized with 50 events having occurred. A second interim analysis will be triggered by the 52nd event. The timing required to analyze the data after the 52nd event is expected to take several months and includes a full review with recommendations by the TIGeR-PaC Data Monitoring Committee. RenovoRx currently anticipates the 52nd event to occur during the second quarter of 2025. The key recommendation from the Data Monitoring Committee on whether or not to continue the study based on the data reviewed is expected to be announced in the second half of 2025.

On April 29, 2025 Immutep Limited(ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported an update on its activities for the quarter ended 31 December 2024 (Q2 FY25) (Press release, Immutep, APR 29, 2025, View Source;v=7bc42bd11d853ed5e8c28f2ffcd6a069ee5cd6b4 [SID1234652261]).

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EFTI DEVELOPMENT PROGRAM FOR CANCERTACTI-004 –Start of Phase III Trial in 1L NSCLC

In December 2024, Immutep initiated its pivotal TACTI-004 Phase III clinical trial of eftilagimod alfa ("efti") for the treatment of first-line metastatic non-small cell lung cancer (1L NSCLC). The receipt of regulatory approval from the Australian Therapeutic Goods Administration means that Immutep has transitioned into a Phase III company; a significant milestone for the Company.

Immutep has successfully completed regulatory submissions in the vast majority of the more than 25 countries that will be part of the global TACTI-004 trial. Additional approvals from multiple countries are expected in the weeks and months ahead. The Company expects to enrol the first patient in Q1 of CY2025.

TACTI-003 (KEYNOTE-C34) –Phase IIb Trial in 1L HNSCC

In December 2024, Immutep reported further positive results from Cohort B of the TACTI-003 (KEYNOTE-C34) Phase IIb trial. Cohort B is evaluating efti in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment of recurrentor metastatic head and neck squamous cell carcinoma patients (1L HNSCC) with PD-L1 negative tumours (CPS <1) who typically do not respond well to anti-PD-1 therapy alone. The results were presented by Martin Forster, M.D., Ph.D., at the ESMO (Free ESMO Whitepaper) Immuno-Oncology (IO) Annual Congress 2024.

Adding to the high response rates and favourable safety data previously reported in July 2024, the new data showed that, encouragingly, median overall survival (OS) has not yet been reached and the 12-month OS rate is 67%. A promising progression-free survival (PFS) of 5.8 months, interim median duration of response (DOR) of 9.3 months, 35.5% objective response rate (ORR) and 58.1% disease control rate (DCR) were also reported. The complete response rate increased to 12.9% and 16.1%, according to RECIST 1.1and iRECIST, respectively. This data compares favourably to historical results from anti-PD-1 therapy alone in 1L HNSCC patients with CPS <1. In addition, efti in combination with KEYTRUDA continues to be well-tolerated with no new safety signals. Immutepwill continue to follow the maturing data from TACTI-003 and engage with regulatory authorities regarding potential paths forward.

AIPAC-003 –Phase II/III Trial in Metastatic Breast Cancer

In October 2024, Immutep completed patient enrolment in the Phase II portion of the AIPAC-003 trial. The randomised Phase II portion of the trial enrolled 65 metastatic hormone receptor positive (HR+), HER2-negative/low or triple-negative breast cancer patients who exhausted endocrine therapy including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Patients across 22 clinical sites in Europe and the United States have been randomised 1:1 to receive either 30mg or 90mg dosing of efti in combination with paclitaxel to determine the optimal biological dose consistent with the FDA’s Project Optimus initiative and prior regulatory interaction with FDA. Data cleaning and analysis is ongoing.

INSIGHT-003 –Phase I Trial in Non-Squamous 1L NSCLC

In November 2024, first overall survival results were reported from the investigator-initiated INSIGHT-003 trial evaluating efti in combination with KEYTRUDA (pembrolizumab) and doublet chemotherapy as first-line treatment for patients with advanced or metastatic non-squamous non-small cell lung cancer (1L NSCLC).

Mature data from patients with a minimum follow-up of 22 months (N=21) demonstrated results significantly exceeding historical controls and expectations. Data included a median OS of 32.9 months, median PFS of 12.7 months, and a 24-month OS rate of 81.0%. Data from all evaluable patients to date (N=40) showed a marked improvement in ORR compared to historical controls. Safety remains favourablewith no new safety signals reported.

Subsequent to quarter end, patient enrolment was completed for INSIGHT-003 in January 2025. The trial reached its enrolment target of approximately 50 evaluable patients across multiple clinical sites in Germany led by the Frankfurt Institute of Clinical Cancer Research IKF. Additional data updates are expected in 2025 and beyond.

EFTISARC-NEO –Phase II Trial in Soft Tissue Sarcoma

Also in November, new data from the EFTISARC-NEO Phase II investigator-initiated trial of efti in combination with radiotherapy plus KEYTRUDA (pembrolizumab) for patients with soft tissue sarcoma (STS) were presented at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting.

Based on preliminary analysis, the triple combination therapy demonstrates significant efficacy in the neoadjuvant setting for resectable STS. The combination achieved a greater than three-fold increase in tumour hyalinization/fibrosis (median 50%) at the time of surgery as compared to a historical median of 15% from radiotherapy alone. In addition to being the primary endpoint of the EFTISARC-NEO study, the tumour hyalinization/fibrosis rate has also been identified as a predictor of overall survival for STS patients in the neoadjuvant setting.

The EFTISARC-NEO trial, with a data cut-off of 20 October 2024, also showed 71.4% of patients achieved a pathologic response defined as ≥35% of hyalinization/fibrosis and 9.5% of patients achieved a complete pathologic response. Additionally, the triple combination therapy is safe with no grade ≥3 toxicities related to efti and KEYTRUDA.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE

IMP761 is a first-in-class agonist LAG-3 antibody designed to restore balance to the immune system by enhancing the "brake" function of LAG-3 to silence dysregulated self-antigen-specific memory T cells that cause many autoimmune diseases.

In December 2024, Immutep reported favourable initial safety data from the placebo-controlled, double-blind first-in-human Phase I study evaluating IMP761. There have been no treatment related adverse events in the first three of five single ascending dosecohorts in healthy participants. Additional safety data and assessment of pharmacokinetic/pharmacodynamic (PK/PD) relationships to follow in the first half of CY2025.

PARTNER ACTIVITY

Collaboration with Monash University

In December 2024, new findings that resolve how human lymphocyte activation gene 3 (LAG-3) binds to its main ligand MHC Class II (MHC-II), also known as HLA Class II (HLA-II) in humans, were published in Science Immunology. The work by Monash University and Immutep, is also the first to show the crystal structure of a human LAG-3/MHC-II complex and provides a better foundation for development of blocking LAG-3 therapeutics, including Immutep’s anti-LAG-3 small molecule program.

INTELLECTUAL PROPERTY

During the quarter, Immutep was granted threenew patents for eftiandIMP761 in various territories. In particular, Immutep was granted a new patent for efti in combination with a PD-1 pathway inhibitor for the treatment of infection from the Brazilian Patent Officeand a new patent for the same combination for the treatment of cancer or infection by the Japan Patent Office. In addition, a new patent was granted for IMP761 by the Malaysian Patent Office.

CORPORATE & FINANCIAL SUMMARY

Board & Senior Management Changes

Independent Non-Executive Director, Anne Anderson, tendered her resignation from the role, effective from 4 October 2024. The Board thanked her for her contribution to Immutep and wished her every success with her next endeavours.

As Immutep’s efti program has advanced into Phase III development, the Company has continued to grow and evolve its team. As part of this, Christian Mueller, who has been with Immutep for over eight years, most recently as SVP Regulatory and Strategy has been promoted to Chief Development Officer. In addition, Dr Florian Vogl, Immutep’s Chief Medical Officer will depart the Company in April 2025. The Company’s current Medical Affairs Advisor, who has been working in different roles closely with Immutep for over nine years, Dr Stephan Winckels, has been appointed acting CMO and taken over all related responsibilities.

Cash Flow Summary

During the quarter, Immutep continued to advance its clinical trial programs for efti and for IMP761. The Company is well funded with a strong cash, cash equivalent and term deposit balance as at 31 December 2024 of approximately A$159.26 million in total, which gives Immutepan expected cash reach to the end of CY2026. The A$159.26 million total balance consists of: 1) a cash and cash equivalent balance of $73.89 million and 2) bank term deposits totalling A$85.37 million, which have been recognised as short-term investments due to having maturities of more than 3 months and less than 12 months.

In Q2 FY25, cash receipts from customers were $8k. The net cash used in G&A activities in the quarter was $566k, compared to $961k in Q1 FY25. Payments to Related Parties (detailed in item 6.1 of the Appendix 4C) comprises Non-Executive Directors’ fees andExecutive Directors’ remuneration of $344k.

The net cash used in R&D activities during the quarter was $16.2 million, compared to $9.5 million to Q1 FY25. The increase is mainly due to the increased level of clinical trial activities especially the commencement of the phase III TACTI-004 clinical trial. Paymentsfor staff costs were$2.5 million in the quarter compared to $2.8 million in Q1 FY25.

Total net cash outflows used in operating activities in the quarter were $19.0 million compared to $8.6 million in Q1 FY25.

Total cash flow used in investing activities for the quarter was $30.4 million, mainly due to the net increase of $30.0 million in short-term investments. The short-term investments are comprised of term deposits with maturities of greater than 3 months and less than 12 months. During the quarter, the company invested $35.3 million inshort-term investments and transferred back $5.3 million from short-term investments that had matured to cash at bank, resulting in anet increase in short-term investments of $30.0 million.

On April 29, 2025 Artios Pharma Limited ("Artios"), a clinical-stage biotech company led by pioneers of DNA damage response ("DDR") drug development, reported encouraging data from its ongoing STELLA Phase 1/2a trial (NCT04657068) in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago (Press release, Artios Pharma, APR 29, 2025, View Source [SID1234652301]). The presentation by Principal Investigator Susanna Ulahannan, MD, Associate Professor, Stephenson Cancer Center at the University of Oklahoma and Director, Drug Development, Sarah Cannon Research Institute (SCRI) at OU Health Stephenson Cancer Center, highlighted the Phase 1/2a clinical data from the STELLA trial of Artios’ lead candidate, ART0380, in combination with low-dose irinotecan in advanced or metastatic solid tumors.

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Artios is pursuing a differentiated clinical development path with its lead product candidate, ART0380, which selectively targets a protein kinase called Ataxia telangiectasia and Rad3-related (ATR). ATR plays a key role in the cellular response to replication stress, a process that can occur endogenously or exogenously, for example via chemotherapy. Many cancers exhibit high endogenous replication stress, such as Ataxia-Telangiectasia Mutated (ATM) protein deficiency found in up to 24% of high-unmet need solid tumors. Artios’ innovative approach exploits replication stress to kill cancer cells through triple targeting: selecting cancers with high replication stress, inducing further replication stress with a low dose of irinotecan, and preventing cellular rescue by inhibiting ATR with ART0380.

"Artios is exploiting a new area of DNA damage response called replication stress with ART0380, and the data from our Phase 1/2a study shows robust clinical activity and good tolerability in a large, identifiable patient population," said Ian Smith, Chief Medical Officer of Artios. "These are unprecedented data for the ATR inhibitor class, and they validate our unique approach of combining ART0380 with a low dose of irinotecan to amplify replication stress. We are encouraged by the incidence and durability of the responses in ATM-deficient cancers, including those of particularly high unmet need, such as pancreatic and colorectal cancer."

Summary of Key Clinical Results:

Artios completed patient enrollment in the dose escalation and initial expansion. As of the data cut-off in February 2025, 87 patients with advanced/metastatic solid tumors who had no satisfactory alternative therapy available to them were treated with ART0380 in combination with low-dose irinotecan, of which 58 patients were treated at the RP2D (recommended Phase 2 dose). These patients’ tumors had varying levels of ATM protein.

The combination treatment at the RP2D showed a meaningful duration of response and prolonged clinical benefit across multiple histologies
37% confirmed overall response rate (cORR) in patients with ATM-negative1 and ATM-low1 cancers (14/38), according to RECIST
50% cORR in ATM-negative cancers (10/20) with a median duration of response (mDoR) of 5.7 months (several responses ongoing)
22% cORR in ATM-low cancers (4/18) with the median duration of response not reached
Responses were observed in 8 different solid tumor types
The combination had a favorable safety profile, was well tolerated, and was shown to be suitable for long-term dosing

The 21-day combination treatment regimen at the RP2D includes administering ART0380 (200mg) on days 1 – 3 and 8 – 10, and irinotecan (60mg/m²) on days 1 and 8.

"The first results from the ongoing STELLA clinical trial are compelling and demonstrate the potential for ART0380-irinotecan combination treatment in ATM biomarker-driven tumors. I am encouraged by the clinical activity and durable responses across multiple cancer indications in heavily pretreated patients, especially considering the complete responses observed in metastatic pancreatic cancer," added Susanna Ulahannan, MD, Director, Drug Development, SCRI at OU Health Stephenson Cancer Center, USA.

The Phase 1/2a trial for ART0380 is conducted with SCRI’s contract research organization, SCRI Development Innovations. Based on the meaningful clinical responses observed, Artios is initiating expansion studies in earlier-line settings, including colorectal and pancreatic cancers, to enable pivotal development of ART0380.

About ART0380

ART0380 is an orally administered, selective small molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR) with first- and best-in-class potential. ATR is activated as the cell’s response to replication stress frequently occurring in rapidly multiplying cells. Inhibiting ATR with ART0380 removes a cancer cell’s ability to repair damaged DNA, leading to the killing of cancerous cells. ART0380 is designed to maximize the therapeutic window and is optimized for combination with DNA damaging therapy to improve patient outcomes. It is currently being evaluated in multiple clinical settings to identify its potential in high replication stress tumors. ART0380 was originally in-licensed by Artios from The University of Texas MD Anderson Cancer Center and ShangPharma Innovation in 2019. The molecule was discovered as part of a collaboration between ShangPharma and MD Anderson’s Therapeutics Discovery Division.

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.