Positive EMERALD Trial Results for Elacestrant Presented at San Antonio Breast Cancer Symposium 2021

- Trial met both primary endpoints demonstrating statistically significant and clinically meaningful extension of progression free survival (PFS) as monotherapy vs. standard of care (SoC) endocrine therapy in overall population and estrogen receptor mutation (mESR1) population

- In the overall population, elacestrant reduced risk of progression or death by 30% vs. SoC

- In the mESR1 population, elacestrant reduced risk of progression or death by 45% vs. SoC

- PFS rate at 12 months with elacestrant was 22.32% versus 9.42% with SoC in the overall population, and 26.76% versus 8.19% in the mESR1 population

- Compared to fulvestrant, elacestrant demonstrated statistically significant PFS and reduced the risk of progression or death by 32% in the overall population and 50% in the mESR1 population

- With these results, elacestrant became the first oral SERD to demonstrate higher efficacy than fulvestrant in a pivotal trial

- Elacestrant was well tolerated and can become standard of care in this patient population

FLORENCE, Italy and BOSTON, Dec. 8, 2021 /CNW/ -- The Menarini Group ("Menarini") and Radius Health, Inc. ("Radius") (NASDAQ: RDUS) (collectively, the "Companies") provided details on the elacestrant data from the EMERALD trial following the positive results presented today at the San Antonio Breast Cancer Symposium (SABCS). The data was presented as a "Late Breaker" and shared in an oral presentation by Dr. Aditya Bardia, MD.

(PRNewsfoto/Menarini Industrie Farmaceutiche Riunite)

The EMERALD trial (NCT03778931), a multicenter, international, randomized, open-label, controlled phase 3 trial evaluated elacestrant as a monotherapy versus SoC for the treatment of ER+/HER2- advanced or mBC. The trial enrolled patients who had received 1 or 2 prior lines of endocrine therapy (ET). Prior progression on an ET plus CDK4/6 inhibitors was mandated for all patients. Up to 1 line of chemotherapy was allowed.

EMERALD met its two primary endpoints: progression-free survival in the overall population and PFS in patients with tumors harboring Estrogen Receptor 1 mutations.

Dr. Aditya Bardia, MD, breast medical oncologist at Mass General Cancer Center, Harvard Medical School and principal investigator of EMERALD, commented, "Patients with pre-treated ER+/HER2- advanced or metastatic breast cancer currently have limited treatment options due to the development of endocrine therapy resistance from earlier treatment lines." Dr. Bardia continued, "Elacestrant – as the first oral SERD – has the potential to become the new standard of care given its performance vs. intramuscular fulvestrant and SoC in the overall population and in the ESR1 patient subgroup. As an oral monotherapy, elacestrant will offer patients, their families, and healthcare providers an efficacious and safe treatment option going forward."

Elcin Barker Ergun, Chief Executive Officer of the Menarini Group, commented, "We are extremely pleased with the results from the EMERALD study. The data appears to demonstrate that elacestrant can create a well tolerated, efficacious oral option vs. fulvestrant and SoC in 2/3 line for patients suffering from advanced or metastatic breast cancer, including those patients with a tumor harboring ESR1 mutations, one of the most difficult to treat subgroups in such cancers. We plan to proceed with regulatory submissions in the United States and European Union in 2022 given the positive safety and efficacy results and thank all patients, their families and healthcare professionals for participating in this important clinical trial."

Menarini plans to pursue combination studies and initiate activity in new lines of therapy such as the adjuvant setting, enabling elacestrant to be utilized in fully addressing the highest unmet needs for ER+/HER2-patients. In 2018, elacestrant received fast track designation from the FDA.

Trial Results:

All patients were mandated to be treated with CDK 4/6 inhibitors. Moreover, patient population characteristics showed that 69.4% of patients had visceral metastasis and 22.2% received chemotherapy. EMERALD met both primary endpoints, which measured PFS of elacestrant as a monotherapy vs. SoC in the overall and mESR1 populations:

• Overall Population
  - Reduced risk of progression or death vs. SoC by 30% (HR=0.697 [95% CI: 0.552, 0.880]; P=0.0018)
  - Extended median PFS by 2.79 months versus SoC of 1.91
  - At 12 months, probability of PFS was 22.3% (95% CI: 15.2%, 29.4%) with elacestrant vs. 9.4% (95% CI: 4.0%, 14.8%) with SoC
  - Compared to fulvestrant, elacestrant reduced risk of progression or death by 32% (HR=0.684 [95% CI: 0.521, 0.897]; P=0.0049)
• ESR1 Mutation Population 
  - Reduced risk of progression or death versus SoC by 45% (HR=0.546 [95% CI: 0.387, 0.768]; P=0.0005) 
  - Extended median PFS by 3.78 months versus SoC of 1.87 
  - At 12 months, probability of PFS was 26.8% (95% CI: 16.2%, 37.4%) with elacestrant vs. 8.2% (95% CI: 1.3%, 15.1%) with SoC 
  - Compared to fulvestrant, elacestrant reduced the risk of progression or death by 50% (HR=0.504 [95% CI: 0.341, 0.741]; P=0.0005)
• In both patient populations, results in key pre-specified subgroups, including visceral metastases, number of prior lines, and geographical region, were consistent with the overall outcome

A key secondary endpoint for the EMERALD trial is Overall Survival (OS). A pre specified interim analysis indicates a trend favoring elacestrant over SoC in both patient groups. Final analysis is expected to occur in late 2022 or early 2023.

Safety Results:

Elacestrant was well tolerated with an encouraging safety profile consistent with other ETs:

• TEAEs leading to discontinuation: infrequent in both elacestrant and SoC arms (6.3% and 4.4%)
• Grade 3 and higher TRAE were 7.2% for elacestrant and 3.1% for SoC
• Grade 3 and higher adverse events for elacestrant: nausea, vomiting and diarrhea were 2.5%, 0.8% and 0%, respectively

A detailed evaluation of data is ongoing and additional results are expected to be published in a peer-reviewed journal.

About Elacestrant (RAD1901) and EMERALD Phase 3 Study

Elacestrant is a selective estrogen receptor degrader (SERD), out-licensed to Menarini Group, which is being evaluated for potential use as a once daily oral treatment in patients with ER+/ HER2- advanced breast cancer. Studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. 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 477 patients who have received prior treatment with one or two lines of endocrine therapy, including a cyclin-dependent kinase (CDK) 4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator's choice of an approved hormonal agent. The primary endpoint of the study is progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. Secondary endpoints include evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR).

About Menarini

The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of $4.2 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 10 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit www.menarini.com.

About Radius

Radius is a global biopharmaceutical company focused on addressing unmet medical needs in the areas of bone health, orphan diseases, and oncology. Radius's lead product, TYMLOS® (abaloparatide) injection, was approved by the U.S. Food and Drug Administration for the treatment of postmenopausal women with osteoporosis at high risk for fracture. The Radius clinical pipeline includes investigational abaloparatide injection for potential use in the treatment of men with osteoporosis; an investigational abaloparatide transdermal system for potential use in the treatment of postmenopausal women with osteoporosis; the investigational drug, elacestrant (RAD1901), for potential use in the treatment of hormone-receptor positive breast cancer out-licensed to Menarini Group; and the investigational drug RAD011, a synthetic cannabidiol oral solution with potential utilization in multiple endocrine and metabolic orphan diseases, initially targeting Prader-Willi Syndrome.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the expected timing of publication of the EMERALD Phase 3 topline results; regulatory submissions in the United States and European Union; and ongoing clinical development activities with respect to elacestrant.

These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the adverse impact the ongoing COVID-19 pandemic is having and is expected to continue to have on our business, financial condition and results of operations, including our commercial operations and sales, clinical trials, preclinical studies, and employees; quarterly fluctuation in our financial results; our dependence on the success of TYMLOS, and our inability to ensure that TYMLOS will obtain regulatory approval outside the U.S. or be successfully commercialized in any market in which it is approved, including as a result of risk related to coverage, pricing and reimbursement; risks related to competitive products; risks related to our ability to successfully enter into collaboration, partnership, license or similar agreements; risks related to clinical trials, including our reliance on third parties to conduct key portions of our clinical trials and uncertainty that the results of those trials will support our product candidate claims; the risk that adverse side effects will be identified during the development of our product candidates or during commercialization, if approved; risks related to manufacturing, supply and distribution; and the risk of litigation or other challenges regarding our intellectual property rights. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, or SEC, including under the caption "Risk Factors" in our Annual Report on Form 10-K for the year ending December 31, 2020 and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

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SOURCE Menarini Industrie Farmaceutiche Riunite

Investor and Media Relations contacts: Menarini: Valeria Speroni Cardi, [email protected]; Radius: Ethan Holdaway, [email protected], [phone]