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As per the findings of the research, up to 25% of post-menopausal women at high risk of developing breast cancer will not benefit from taking the medication MFT scientists developed a hormone blood test which can determine the effectiveness of anastrozole. (Credit: Nappy on Unsplash) Scientists at Manchester University NHS Foundation Trust (MFT) have developed a new highly sensitive hormone blood test to assess the efficacy of the preventative breast cancer drug, anastrozole. Anastrozole is currently the recommended preventative therapy for women in the post-menopausal stage who are at high risk of developing breast cancer. MFT published the findings of the research in the Lancet Oncology journal. The research demonstrated that up to 25% of these post-menopausal women will not benefit from taking the medication. It also showed that clinicians will be able to provide these patients with a customised treatment plan if they conduct routine hormone testing. This will prevent thousands of women from experiencing negative effects of the drug, the NHS trust said. According to the study, anastrozole would have little to no effect on a woman’s risk of breast cancer if her oestradiol levels were low. As a result, these women might have avoided the medication’s potential five-year adverse effects, which frequently include hot flushes, pains, and low mood. MFT medical genetics and cancer epidemiology consultant D Gareth Evans said: “These results indicate the importance of incorporating serum oestrogen levels into risk models, so women can be reassured despite other risk factors if their levels are low, and likewise, higher levels may make more women eligible for anastrozole.” In postmenopausal women, anastrozozole reduces oestrogen levels, which would otherwise promote the growth of breast cancer cells. The once daily 1mg tablet of the hormone therapy medication known to be an aromatase inhibitor is administered over five years. It can only be taken by women who have gone through menopause as the medication cannot reduce oestrogen in women whose ovaries are still functioning. Anastrozole has been suggested as a preventive treatment by the National Institute for Health and Care Excellence (NICE) since 2017. The Medicines and Healthcare Products Regulatory Agency (MHRA) granted the medication a licence for use on the NHS in November 2023. It was based on results from an earlier study from the IBIS-II preventive trial, which was funded by MFT researchers. The trial revealed that anastrozole lowers the incidence of breast cancer in postmenopausal women who are at increased risk by 49%.

Wyost® (denosumab-bddz) and Jubbonti® (denosumab-bddz) interchangeable with and approved by FDA for all indications of reference medicines Xgeva ®* (denosumab) and Prolia®* (denosumab) FDA approval based on robust clinical studies and totality of evidence, which show no clinically meaningful differences from reference medicines March 5, 2024 – Sandoz, the global leader in generic and biosimilar medicines, today announced that the US Food and Drug Administration (FDA) approved Wyost® (denosumab-bbdz) and Jubbonti® (denosumab-bbdz), the first and only FDA-approved denosumab biosimilars, to treat all indications of the reference medicines. Keren Haruvi, President Sandoz North America, said: "Sandoz has achieved the first FDA approval for biosimilars to denosumab, a medicine that can address primary and secondary bone loss, such as osteoporosis, as well as cancer-related skeletal events, which are disease states that can profoundly reduce quality of life for patients. I am proud that Sandoz continues to pioneer access to these life-changing medicines for the patients who need them most." Wyost® is approved to prevent skeletal-related events (SREs) in patients with multiple myeloma and in patients with bone metastases from solid tumors, to treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.1 Bone is the third most frequent site for metastatic tumors.2 Nearly all types of cancer can spread to the bone and cause pain and fractures, though cancers that often metastasize in bones include breast and prostate.3 Jubbonti® is approved to treat postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, to treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.4 Osteoporosis is a bone disease that develops when bone mineral density and bone mass decrease or when bone strength and structure change. People living with osteoporosis typically do not have symptoms and might not know they have the disease until they experience a fracture. More than 10 million US adults aged 50 and over live with osteoporosis, a major cause of fractures in postmenopausal women and in older men.5,6 Half of all women over the age of 50 will experience an osteoporotic fracture during their lifetime.7 The FDA approval is based on robust clinical studies and accompanied by labeling with safety warnings. The Jubbonti® approval is also accompanied by approval of Sandoz’s Jubbonti® Risk Evaluation and Mitigation Strategy (REMS) program, which is designed to inform prescribers and patients about the risk of severe hypocalcemia associated with Jubbonti® in patients with advanced chronic kidney disease, including dialysis-dependent patients. Wyost® and Jubbonti® have the same dosage form, route of administration, dosing regimen and presentation as the respective reference medicines. Wyost® and Jubbonti® are approved as interchangeable with the reference medicines for all indications. Given ongoing patent litigation around these products, Sandoz will not comment on anticipated launch timing or other launch details at this time. Wyost® 120 mg/1.7 mL (70 mg/mL) injection has been approved by the FDA as interchangeable with the reference medicine, a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue).8,9 Wyost® is indicated in the US to prevent SREs in patients with multiple myeloma and in patients with bone metastases from solid tumors, to treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.1 Jubbonti® 60 mg/1 mL injection has been approved by the FDA as interchangeable with the reference medicine, a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue).8,9 Jubbonti® is indicated in the US to treat postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, to treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.4 References 1. Wyost®. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761362s000lbl.pdf [Last accessed: March 2024] 2. Bone Metastasis. Apoorva Jayarangaiah; Alysia K. Kemp; Pramod Theetha Kariyann, Oct 25 2022. Available at https://www.ncbi.nlm.nih.gov/books/NBK507911/#:~:text=The%20skeleton%20is%20the%20third,metastasize%20to%20bone%20as%20well. [Last accessed: March 2024] 3. American Cancer Society. Bone Metastases. Available at: https://www.cancer.org/treatment/understanding-your-diagnosis/advanced-cancer/bone-metastases.html [Last accessed: March 2024] 4. Jubbonti®. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761362s000lbl.pdf [Last accessed: March 2024] 5. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoporosis. 2022. Available at: https://www.niams.nih.gov/health-topics/osteoporosis [Last accessed: March 2024] 6. National Center for Health Statistics. Osteoporosis or Low Bone Mass in Older Adults: United States, 2017–2018. 2021. Available at: https://www.cdc.gov/nchs/products/databriefs/db405.htm [Last accessed: March 2024] 7. Bone Health and Osteoporosis Foundation. Osteoporosis Fast Facts. Available at: https://www.bonehealthandosteoporosis.org/wp-content/uploads/Osteoporosis-Fast-Facts-2.pdf [Last accessed: March 2024] 8. Amgen Inc. Prolia® (Denosumab): Prescribing Information. Available at: https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Prolia/prolia_pi.pdf [Last accessed: March 2024] 9. Amgen Inc. Xgeva® (Denosumab): Prescribing Information. Available at: https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/xgeva/xgeva_pi.pdf [Last accessed: March 2024] Sandoz (SIX: SDZ; OTCQX: SDZNY) is the global leader in generic and biosimilar medicines, with a growth strategy driven by its Purpose: pioneering access for patients. 22,000 people of more than 100 nationalities work together to bring Sandoz medicines to some 500 million patients worldwide, generating substantial global healthcare savings and an even larger total social impact. Its leading portfolio of more than 1500 products addresses diseases from the common cold to cancer. Headquartered in Basel, Switzerland, Sandoz traces its heritage back to the year 1886. Its history of breakthroughs includes Calcium Sandoz in 1929, the world’s first oral penicillin in 1951, and the first biosimilar in 2006. In 2022, Sandoz achieved sales of USD 9.1 billion and core EBITDA of USD 1.9 billion. 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Data published in Molecular Cancer Therapeutics describes the scientific background underlying the design, discovery and optimization of palazestrant (OP-1250)Pre-clinical results demonstrate that palazestrant, as both a CERAN and a SERD, has a highly differentiated mechanism of action as a potential therapy for advanced ER+/HER2- breast cancer SAN FRANCISCO, March 06, 2024 (GLOBE NEWSWIRE) -- Olema Pharmaceuticals, Inc. (“Olema” or “Olema Oncology,” Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, today announced that Molecular Cancer Therapeutics, an American Association for Cancer Research journal, has selected as a featured article a data publication that describes the distinct properties of palazestrant (OP-1250). The paper, titled “Palazestrant (OP-1250), a Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination”, describes the scientific background underlying the design, discovery and optimization of palazestrant. “The research described in this paper reviews the deliberate design and processes used in discovering and optimizing palazestrant as a molecule purpose-built to address a crucial unmet need in the treatment of women’s cancers, and we are delighted that Molecular Cancer Therapeutics has featured our work,” said David C. Myles, Ph.D., Olema’s Chief Discovery and Non-Clinical Development Officer. “What’s even more exciting is to see how faithfully the pre-clinical research predicted the behavior of palazestrant now that it is in late-stage clinical development. We saw the potential then, as told in the paper, and we believe that every day brings us closer to having a real impact transforming the treatment paradigm for women with cancer.” As part of the discovery and optimization process, palazestrant was assessed across an extensive series of biochemical, cell culture, and in vivo assays comparing it with other antiestrogens and compounds that are either approved for use by the FDA or are currently in clinical development, including aromatase inhibitors, selective ER modulators (SERMs), traditional SERDs, and proteolysis-targeting chimeras (PROTACs). As a CERAN, palazestrant has a distinct mechanism of action (MOA), and though it actively degrades the ER, the paper shows that degradation alone is not a reliable mechanism to drive the efficacy of an endocrine agent. In mouse xenograft models, palazestrant demonstrated excellent pharmacokinetics, was well tolerated, showed synergy with CDK4/6 inhibitors, and was highly effective at reducing tumor growth in both wild-type and ESR1-mutant ER+ breast cancer. In addition, in an ESR1-mutant intercranial xenograft model, palazestrant inhibited tumor growth and improved survival of animals with CNS metastases, even after stopping drug treatment. The paper can be accessed in the latest print edition of Molecular Cancer Therapeutics or online at https://aacrjournals.org/mct/article/doi/10.1158/1535-7163.MCT-23-0351/731746/Palazestrant-OP-1250-a-Complete-Estrogen-Receptor. About Palazestrant (OP-1250) Palazestrant (OP-1250) is a novel, orally-available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In clinical studies, palazestrant completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer and has demonstrated anti-tumor efficacy along with attractive pharmacokinetics and exposure, favorable tolerability, CNS penetration, and combinability with CDK4/6 inhibitors. Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is currently being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib) and a PI3Ka inhibitor (alpelisib). For more information, please visit www.opera01study.com. About Olema Oncology Olema Oncology is a clinical-stage biopharmaceutical company committed to transforming the standard of care and improving outcomes for women living with cancer. Olema is advancing a pipeline of novel therapies by leveraging our deep understanding of endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance. In addition to our lead product candidate, palazestrant (OP-1250), a proprietary, orally-available complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD), Olema is developing a potent KAT6 inhibitor. Olema is headquartered in San Francisco and has operations in Cambridge, Massachusetts. For more information, please visit us at www.olema.com. Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Words such as “anticipate,” “expect,” “will,” “may,” “goal,” “potential” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements include those related to Olema’s preclinical program, including the potential beneficial characteristics of palazestrant (OP-1250), both as a monotherapy and in combination with CDK4/6 inhibitors, palazestrant’s potential to address to address an unmet need in the treatment of women’s cancers, and palazestrant’s ability to transform the treatment paradigm for women with cancer. Because such statements deal with future events and are based on Olema’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of Olema could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, those discussed in the section titled “Risk Factors” in Olema’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, and future filings and reports that Olema makes from time to time with the U.S. Securities and Exchange Commission. Except as required by law, Olema assumes no obligation to update these forward-looking statements, including in the event that actual results differ materially from those anticipated in the forward-looking statements. Contact:Geoffrey Mogilner, Vice President, Investor Relations and Communicationsir@olema.com