• ORSERDU (elacestrant) was approved by the FDA in January 2023 for estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with ESR1-mutations (ESR1-mut) that are found in up to 40% of tumors
   
• In patients whose tumors harbor ESR1-mut, a previous post-hoc subgroup analysis demonstrated that for those with prior CDK4/6 inhibitor (CDK4/6i) exposure of at least 12 months, second-line treatment with elacestrant resulted in a median progression free survival (PFS) of 8.6 months, compared to 1.9 months on standard of care (SOC).
   
• This new post-hoc subgroup analysis expands our understanding of a potential role for elacestrant in patients with ER+/HER2- breast cancer with Non-Detected ESR1-mut. Patients who progressed within six months of CDK4/6i therapy achieved a median PFS of 5.32 months with elacestrant vs. 1.87 months with SOC.
   
• These data, while exploratory, further build upon our understanding of elacestrant as an oral endocrine therapy in the second-line metastatic breast cancer setting.

FLORENCE (Italy) and New York, NY, May 26, 2023 – The Menarini Group (“Menarini”), a leading Italian pharmaceutical and diagnostics company, and Stemline Therapeutics (“Stemline”), a wholly-owned subsidiary of the Menarini Group, today announced results from a new analysis of the pivotal EMERALD clinical study that suggest that oral single-agent elacestrant may be effective in ER+, HER2- advanced or metastatic breast cancer patients with Non-Detected ESR1-mut whose disease has progressed within six months of treatment with a CDK4/6i. Results from this new post-hoc subgroup analysis will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.

EMERALD is a Phase 3 registrational trial that demonstrated statistically significant PFS with elacestrant versus SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane). Based on these results, the U.S. Food & Drug Administration (FDA) approved ORSERDU (elacestrant) on January 27, 2023, for the treatment of postmenopausal women or adult men with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. ESR1 mutations are present in up to 40% of ER+, HER2- advanced or metastatic breast cancers, and they are a known driver of resistance to standard endocrine therapy.

Importantly, a previous subgroup analysis of the EMERALD PFS results, which were presented at the San Antonio Breast Cancer Symposium (SABCS) 2022, demonstrated that the duration of prior CDK4/6i treatment was positively associated with longer PFS on elacestrant but not with SOC. For patients with ESR1-mut who were treated with CDK4/6i for ≥12 months prior to randomization on EMERALD, elacestrant achieved a median PFS of 8.6 months versus 1.9 months on SOC, with an absolute difference of 6.7 months, and a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63).

In this new analysis to be presented at ASCO 2023, researchers evaluated treatment with elacestrant in a subgroup of patients with Non-Detected ESR1-mut enrolled in the EMERALD study with rapidly progressing disease. Results for patients whose disease progressed within six months of CDK4/6i therapy demonstrated a median PFS of 5.32 months for the elacestrant arm, compared to 1.87 months for patients who received SOC (HR 0.518; 95% CI: 0.216-1.165).

“Endocrine therapy given in combination with a CDK4/6 inhibitor is a mainstay in ER+/HER2- metastatic breast cancer for first-line treatment. It is encouraging to see that patients with ESR1-mutations who had a longer duration of prior CDK4/6i therapy, when treated subsequently with elacestrant, had 8.6 months of median PFS versus 1.9 months with the standard of care, as we published at SABCS in December 2022. Until now, elacestrant’s potential benefit in patients with Non-Detected ESR1-mutations was an open question. The results presented at ASCO 2023, while exploratory, suggest that treatment with oral elacestrant following disease progression within six months of CDK4/6i treatment for Non-Detected ESR1-mutations may provide clinical benefit for these patients, and warrant further study,” said Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center.

Safety data were consistent with previously reported results. Most adverse events (AEs), including nausea, were grade 1 and 2, and no grade 4 treatment-related AEs (TRAEs) were reported. Only 3.4% of patients receiving elacestrant and 0.9% receiving SOC discontinued therapy due to any TRAE. No deaths assessed as treatment-related were reported in either arm. No hematologic safety signal was observed, and none of the patients in either treatment arm had sinus bradycardia.

“At Menarini Group, we are focused on developing innovative solutions that address the greatest unmet needs in cancer treatments,” said Elcin Barker Ergun, CEO of the Menarini Group. “ORSERDU represents an important step towards that, providing the first and only FDA-approved oral endocrine therapy after 20 years, for advanced or metastatic ER+/HER2- tumors with ESR1 mutations. This new data advances our understanding of further potential areas where elacestrant may help patients living with metastatic breast cancer who have limited treatment options.”

2023 ASCO Annual Meeting Presentation Details
Abstract Title: Oral elacestrant vs standard-of-care in estrogen receptor-positive, HER2-negative (ER+/HER2-) advanced or metastatic breast cancer (mBC) without detectable ESR1 mutation (EMERALD): Subgroup analysis by prior duration of CDK4/6i plus endocrine therapy (ET)
Abstract #: 1070 | Poster Bd #: 291
Session Title: Breast Cancer – Metastatic
Session Date and Time: June 4, 2023; 8:00AM CDT, Hall A
Presentation Type: Poster

About the EMERALD Phase 3 Study (NCT03778931)
The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator's choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. In the group of patients whose tumors had ESR1 mutations, elacestrant achieved a median PFS of 3.8 months vs 1.9 months on the SOC, and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC.

About ORSERDU® (elacestrant)

Indication
ORSERDU (elacestrant), 345 mg tablets, is approved by the U.S. Food & Drug Administration (FDA) for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Full prescribing information can be found at www.orserdu.com

Important Safety Information, ORSERDU®
Warnings and Precautions

• Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity

• Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose.

Adverse Reactions

• Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).

• The most common adverse reactions (≥10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite (15%), diarrhea (13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug Interactions

• Concomitant use with CYP3A4 inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in Specific Populations

• Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.

• Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).

• The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or via email at StemlinePVG.SM@ppd.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The Marketing Authorization Application (MAA) is currently under review by the European Medicines Agency (EMA).

Elacestrant is also being investigated in several clinical trials in metastatic breast cancer disease, alone or in combination with other therapies: ELEVATE (NCT05563220); ELECTRA (NCT05386108); and ELCIN (NCT05596409). Elacestrant is also planned to be evaluated in early breast cancer disease.

The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc. The Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant.

About The Menarini Group
The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit www.menarini.com.

About Stemline Therapeutics
Stemline Therapeutics, a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the United States, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs), a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the US and EU to date. Stemline also commercializes Nexpovio® in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers.

Media Contacts
The Menarini Group
Valeria Speroni Cardi
Email: pressoffice@menarini.com

Stemline Therapeutics, Inc.
Cheya Pope
Email: cpope@stemline.com