Monte Rosa Therapeutics Announces Clinical Supply Agreement to Support Phase 2 Trial Evaluating MRT-2359 in Combination with Apalutamide for the Treatment of Metastatic Castration-Resistant Prostate Cancer

MRT-2359 is an investigational, orally bioavailable, GSPT1-directed molecular glue degrader that has shown compelling clinical activity in combination with androgen receptor (AR) inhibition in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) patients with AR mutations in an ongoing Phase 1/2 clinical study 

Monte Rosa plans to initiate a new, signal-confirming Phase 2 study of MRT-2359 in combination with apalutamide targeting AR mutant patients in Q3 2026

BOSTON, March 16, 2026 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (NASDAQ:GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced the company has entered into a supply agreement with Johnson & Johnson to evaluate MRT-2359 in combination with ERLEADA® (apalutamide) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with androgen receptor (AR) mutations in a planned Phase 2 study expected to initiate in the third quarter of 2026. MRT-2359 is an investigational, orally bioavailable, GSPT1-directed MGD discovered and developed by Monte Rosa. ERLEADA® is an AR inhibitor developed by Janssen Research and Development, LLC, indicated for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) and patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

Under the terms of the agreement, Monte Rosa will conduct and sponsor the trial and Johnson & Johnson will provide ERLEADA® as part of a supply agreement.

"We are pleased to enter into this supply agreement with Johnson & Johnson to further explore the potential of MRT-2359 in combination with next-generation AR inhibitors such as apalutamide in patients with advanced prostate cancer," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "Based on the compelling clinical activity observed to date in heavily pretreated patients with AR mutations, we believe this combination approach holds significant promise. Data generated from these studies have the potential to further confirm MRT-2359's clinical activity and may position the program for advancement into registrational studies, representing an important step forward for prostate cancer patients with limited therapeutic options for this respective patient population."

The planned Phase 2 study of up to 25 mCRPC patients is designed to efficiently assess the efficacy and safety of MRT-2359 plus ERLEADA® in mCRPC patients with AR mutations, with potential to expand the study into additional patient subsets, including patients naïve to next-generation AR inhibitors, should the activity in the AR mutant patient population confirm. The study will evaluate PSA response, RECIST response, duration of response, progression-free survival (PFS), radiographic progression-free survival (rPFS), and safety.

Monte Rosa recently announced additional, positive data from the company's ongoing Phase 1/2 clinical study evaluating MRT-2359 in combination with enzalutamide in heavily pretreated patients with mCRPC. The data were presented at the 2026 ASCO Genitourinary (GU) Cancers Symposium on February 26, 2026.

About MRT-2359

MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) of GSPT1. MYC-driven cancers, including prostate cancer, depend on enhanced translation of oncoproteins to support rapid growth. MRT-2359 exploits this therapeutic vulnerability by disrupting translation through selective degradation of the translation termination factor GSPT1. MRT-2359 treatment reduced cellular abundance of many prostate cancer-relevant oncoproteins, including AR, MYC, and Cyclin D1-E2F, and demonstrated robust anti-tumor activity across multiple preclinical models of metastatic castration-resistant prostate cancer (mCRPC). MRT-2359 in combination with the AR inhibitor enzalutamide is being investigated in an ongoing Phase 1/2 study (clinicaltrials.gov identifier NCT05546268) in patients with mCRPC. In heavily pretreated mCRPC patients, MRT-2359 plus enzalutamide demonstrated encouraging early signals of clinical response.

About Monte Rosa

Monte Rosa Therapeutics is a clinical-stage biotechnology company developing highly selective molecular glue degrader (MGD) medicines for patients living with serious diseases. MGDs are small molecule protein degraders that have the potential to treat many diseases that other modalities, including other degraders, cannot. Monte Rosa's QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates) discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology, and proteomics to rationally design MGDs with unprecedented selectivity. Monte Rosa has developed the industry's leading pipeline of first-in-class and only-in-class MGDs, spanning autoimmune and inflammatory diseases, oncology, and beyond, with three programs in the clinic. Monte Rosa has ongoing collaborations with leading pharmaceutical companies in the areas of immunology, oncology and neurology. For more information, visit www.monterosatx.com.

ERLEADA^® IMPORTANT SAFETY INFORMATION 

WARNINGS AND PRECAUTIONS 

Cerebrovascular and Ischemic Cardiovascular Events — In a randomized study (SPARTAN) of patients with nmCRPC, ischemic cardiovascular events occurred in 3.7% of patients treated with ERLEADA^® and 2% of patients treated with placebo. In a randomized study (TITAN) in patients with mCSPC, ischemic cardiovascular events occurred in 4.4% of patients treated with ERLEADA^® and 1.5% of patients treated with placebo. Across the SPARTAN and TITAN studies, 4 patients (0.3%) treated with ERLEADA^® and 2 patients (0.2%) treated with placebo died from an ischemic cardiovascular event. Patients with history of unstable angina, myocardial infarction, congestive heart failure, stroke, or transient ischemic attack within 6 months of randomization were excluded from the SPARTAN and TITAN studies. 

In the SPARTAN study, cerebrovascular events occurred in 2.5% of patients treated with ERLEADA^® and 1% of patients treated with placebo. In the TITAN study, cerebrovascular events occurred in 1.9% of patients treated with ERLEADA^® and 2.1% of patients treated with placebo. Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA^®, and 2 patients (0.2%) treated with placebo died from a cerebrovascular event. 

Cerebrovascular and ischemic cardiovascular events, including events leading to death, occurred in patients receiving ERLEADA^®. Monitor for signs and symptoms of ischemic heart disease and cerebrovascular disorders. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Consider discontinuation of ERLEADA^® for Grade 3 and 4 events. 

Fractures — In a randomized study (SPARTAN) of patients with nmCRPC, fractures occurred in 12% of patients treated with ERLEADA^® and in 7% of patients treated with placebo. In a randomized study (TITAN) of patients with mCSPC, fractures occurred in 9% of patients treated with ERLEADA^® and in 6% of patients treated with placebo. Evaluate patients for fracture risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. 

Falls — In a randomized study (SPARTAN), falls occurred in 16% of patients treated with ERLEADA^® compared with 9% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Falls occurred in patients receiving ERLEADA^® with increased frequency in the elderly. Evaluate patients for fall risk. 

Seizure — In two randomized studies (SPARTAN and TITAN), 5 patients (0.4%) treated with ERLEADA^® and 1 patient treated with placebo (0.1%) experienced a seizure. Permanently discontinue ERLEADA^® in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA^®. Advise patients of the risk of developing a seizure while receiving ERLEADA^® and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. 

Severe Cutaneous Adverse Reactions — Fatal and life-threatening cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) occurred in patients receiving ERLEADA^®. 

Monitor patients for the development of SCARs. Advise patients of the signs and symptoms of SCARs (eg, a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy). If a SCAR is suspected, interrupt ERLEADA^® until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, or for other Grade 4 skin reactions, permanently discontinue ERLEADA^® [see Dosage and Administration (2.2)].

Interstitial Lung Disease (ILD)/Pneumonitis — Fatal and life-threatening interstitial lung disease (ILD) or pneumonitis can occur in patients treated with ERLEADA^®.

Post-marketing cases of ILD/pneumonitis, including fatal cases, occurred in patients treated with ERLEADA^®. Across clinical trials (TITAN and SPARTAN, n=1327), 0.8% of patients treated with ERLEADA^® experienced ILD/pneumonitis, including 0.2% who experienced Grade 3 events [see Adverse Reactions (6.1, 6.2)].

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold ERLEADA^® if ILD/pneumonitis is suspected. Permanently discontinue ERLEADA^® in patients with severe ILD/pneumonitis or if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.2)].

Embryo-Fetal Toxicity — The safety and efficacy of ERLEADA^® have not been established in females. Based on findings from animals and its mechanism of action, ERLEADA^® can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA^® [see Use in Specific Populations (8.1, 8.3)]. 

ADVERSE REACTIONS 

The most common adverse reactions (≥10%) that occurred more frequently in the ERLEADA^®-treated patients (≥2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture. 

Laboratory Abnormalities — All Grades (Grade 3-4) 

• Hematology — In the TITAN study: white blood cell decreased ERLEADA^® 27% (0.4%), placebo 19% (0.6%). In the SPARTAN study: anemia ERLEADA^® 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA^® 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA^® 41% (1.8%), placebo 21% (1.6%)
  • Chemistry — In the TITAN study: hypertriglyceridemia ERLEADA^® 17% (2.5%), placebo 12% (2.3%). In the SPARTAN study: hypercholesterolemia ERLEADA^® 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA^® 70% (2%), placebo 59% (1.0%); hypertriglyceridemia ERLEADA^® 67% (1.6%), placebo 49% (0.8%); hyperkalemia ERLEADA^® 32% (1.9%), placebo 22% (0.5%) 
    
    
    
    

Rash — In 2 randomized studies (SPARTAN and TITAN), rash was most commonly described as macular or maculopapular. Adverse reactions of rash were 26% with ERLEADA^® vs 8% with placebo. Grade 3 rashes (defined as covering >30% body surface area [BSA]) were reported with ERLEADA^® treatment (6%) vs placebo (0.5%). 

The onset of rash occurred at a median of 83 days. Rash resolved in 78% of patients within a median of 78 days from onset of rash. Rash was commonly managed with oral antihistamines, topical corticosteroids, and 19% of patients received systemic corticosteroids. Dose reduction or dose interruption occurred in 14% and 28% of patients, respectively. Of the patients who had dose interruption, 59% experienced recurrence of rash upon reintroduction of ERLEADA^®. 

Hypothyroidism — In 2 randomized studies (SPARTAN and TITAN), hypothyroidism was reported for 8% of patients treated with ERLEADA^® and 1.5% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA^® and 7% of patients treated with placebo. The median onset was at the first scheduled assessment. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose adjusted. 

DRUG INTERACTIONS 

Effect of Other Drugs on ERLEADA^® — Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties. No initial dose adjustment is necessary; however, reduce the ERLEADA^® dose based on tolerability [see Dosage and Administration (2.2)]. 

Effect of ERLEADA^® on Other Drugs 

CYP3A4, CYP2C9, CYP2C19, and UGT Substrates — ERLEADA^® is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA^® with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued. Concomitant administration of ERLEADA^® with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure. Use caution if substrates of UGT must be co-administered with ERLEADA^® and evaluate for loss of activity. 

P-gp, BCRP, or OATP1B1 Substrates — Apalutamide is a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. Concomitant use of ERLEADA^® with medications that are substrates of P-gp, BCRP, or OATP1B1 can result in lower exposure of these medications. Use caution if substrates of P-gp, BCRP, or OATP1B1 must be co-administered with ERLEADA^® and evaluate for loss of activity if medication is continued. 

Please see the full Prescribing Information for ERLEADA^®. 

Forward-Looking Statements

This communication includes express and implied "forward-looking statements," including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts and in some cases, can be identified by terms such as "may," "might," "will," "could," "would," "should," "expect," "intend," "plan," "objective," "anticipate," "believe," "estimate," "predict," "potential," "continue," "ongoing," or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained herein include, but are not limited to, statements about our ability to grow our product pipeline, our ability to successfully complete research and further development and commercialization of our drug candidates in current or future indications, including the timing and results of our clinical trials and our ability to conduct and complete clinical trials, statements regarding the compelling clinical activity of MRT-2359 in combination with AR inhibition in heavily pretreated mCRPC patients with AR mutations in our ongoing Phase 1/2 clinical study, statements regarding our ability to further explore the potential of MRT-2359 due to the supply agreement, our expectations regarding the clinical activity observed with MRT-2359 in combination with enzalutamide in heavily pretreated mCRPC patients that may position the program for advancement into registrational studies, representing an important step forward for prostate cancer patients with limited therapeutic options, our plans to initiate a signal-confirming Phase 2 study evaluating MRT-2359 in combination with apalutamide targeting AR mutant patients in 2026, our expectations regarding the potential to expand the planned Phase 2 study into additional patient subsets, including patients naïve to next-generation AR inhibitors, the clinical significance of the clinical data read-out at upcoming scientific meetings and timing thereof, statements around our ability to capitalize on and potential benefits resulting from our research and translational insights, among others. By their nature, these statements are subject to numerous risks and uncertainties, including those risks and uncertainties set forth in our most recent Annual Report on Form 10-K for the year ended December 31, 2024, filed with the U.S. Securities and Exchange Commission on March 20, 2025, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance, or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations, or otherwise, except as required by applicable law. Certain information contained in these materials and any statements made orally during any presentation of these materials that relate to the materials or are based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of these materials, we have not independently verified, and make no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in these materials relating to or based on such internal estimates and research.

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