EGF

NERLYNX® (neratinib) has been approved as a single agent for the treatment of early-stage HER2+ breast cancer, and in combination with capecitabine for the treatment of advanced or metastatic HER2+ breast cancer[1] Approval coincides with the first appointment of field force employees, signifying the growth of Specialised Therapeutics in Thailand SINGAPORE, Feb. 11, 2025 /PRNewswire/ -- A NEW breast cancer therapy shown to significantly reduce the risk of cancer recurrence and improve disease-free survival in women is now approved for use in Thailand.[1,2,3] NERLYNX® (neratinib), an oral medication, has been approved by the Thailand Food and Drug Administration (Thailand FDA) as a single agent "for the extended adjuvant treatment of adult patients with early-stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who completed adjuvant trastuzumab-based therapy less than one year ago."[1] Additionally, NERLYNX has been approved in combination with capecitabine"for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting."[1] In early breast cancer, NERLYNX has been shown to significantly reduce the ongoing risk of recurrence in women positive for human epidermal growth factor receptor 2 (HER2+), with the greatest benefit seen in women who are also hormone-receptor positive (HR+) and who commence therapy within 12 months of completing trastuzumab-based therapy.[2,3] For these women, the five-year risk of recurrence is reduced by up to 42%.[4] In women with advanced or metastatic HER2+ breast cancer, NERLYNX in combination with capecitabine (N+C) was found to significantly improve mean progression free survival (PFS) by 2.2 months over treatment with lapatinib plus capecitabine (L+C).[5] The duration of treatment response was longer for patients administered N+C (8.5 months) versus L+C (5.6 months), while the risk of disease progression or death was reduced by up to 24% among those treated with N+C at a median follow-up of 30 months.[5,6] NERLYNX is being made available in Thailand by independent pharmaceutical company, Specialised Therapeutics (ST), under exclusive license from Puma Biotechnology, Inc. ST Chief Executive Officer, Mr Carlo Montagner, said the approval of NERLYNX in Thailand was an important milestone for the company. "We are proud to have obtained approval of NERLYNX in Thailand for adults with HER2 positive breast cancer. This is a significant milestone for Specialised Therapeutics, but importantly also for women diagnosed with breast cancer in Thailand who will be presented with an opportunity to access a treatment that will help reduce the risk of disease recurrence and improve outcomes, in either the early or advanced stages of their disease." Breast cancer is the most common cancer diagnosed in Thai women, and the second leading cause of cancer mortality in females, behind liver cancer.[7] The incidence of breast cancer in Thailand has been rising at an alarming rate, with the annual age-standardised incidence rate doubling over the past 20 years (from 17.8/100,000 in 1998, to 35.7/100,000 in 2020).[8,9] In 2022, 21,628 Thai women were newly diagnosed with breast cancer, accounting for almost a quarter (23.2%) of all new cancer diagnoses in females.[7] Coinciding with the NERLYNX approval, ST is also pleased to announce the growth of its Thailand office, with new field force members due to join the company in March 2025. "We are extremely excited about the new journey we are undertaking in Thailand," said Mr Montagner. "Hiring our first field force employees, who have an extensive understanding of the local healthcare landscape, enables us to connect with oncologists around the country at the earliest opportunity, ahead of launching NERLYNX and making it available for eligible breast cancer patients as soon as possible. "As we continue to seek approvals for our strong pipeline of specialised medicines and technologies, we remain committed to meeting the needs of patients with rare diseases across Thailand, and making a difference to their lives. We look forward to working with the Thailand FDA and local specialists as we endeavour to provide timely access to these new treatments for the patients that need them." Ends. About NERLYNX NERLYNX (neratinib) is an irreversible tyrosine kinase inhibitor (TKI) that blocks signal transduction through the epidermal growth factor receptors, HER1, HER2 and HER4.[10] It is an oral tablet and works by binding to multiple receptors inside the cancer cell, blocking signals that tell cancer cells to grow and multiply.[11,12] NERLYNX has received approval for the treatment of certain patients with extended adjuvant and/or metastatic HER2-positive breast cancer in more than 40 countries outside the United States (US), including the European Union (EU), China, Latin America, Australia, Canada, and Hong Kong. About HER2-Positive (HER2+) Breast Cancer Approximately 20-25% of breast cancer tumours over-express the HER2 protein. HER2-positive (HER2+) breast cancer is a highly heterogeneous tumour that is often more aggressive than other types of breast cancer and has a poor prognosis, increasing the risk of disease progression and death.[10,13,14] While trastuzumab has helped to improve the survival and prognosis of patients with HER2+ breast cancer, around 20-30% of patients will experience recurrence and metastases after trastuzumab targeted therapy.[14] About the ExteNET Study[2-4,15] The ExteNET trial was a double-blind, placebo-controlled, Phase III trial of neratinib versus placebo after adjuvant treatment with trastuzumab (Herceptin) in patients with early-stage HER2-positive breast cancer. The ExteNET trial randomised 2,840 patients in 41 countries with early-stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomised to receive neratinib or placebo for a period of one year. Patients were then followed for recurrent disease, ductal carcinoma in situ (DCIS), or death for a period of five years after randomisation. The primary endpoint of the trial was invasive disease-free survival (iDFS). The trial demonstrated that after a median follow up of 5.2 years, treatment with neratinib resulted in a 27% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.73, p = 0.008). The 5-year iDFS rate for the neratinib arm was 90.2%, versus 87.7% for the placebo arm. An additional five-year sub-group analysis demonstrated a 42% reduction in risk of recurrence and 59% reduction in risk of CNS recurrence or death of any cause in women who were HR+ and who had commenced neratinib therapy within 12 months of completing treatment with trastuzumab. The most common adverse reactions (≥ 5%) were diarrhoea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased and urinary tract infection. About the NALA Study[5,6] The NALA trial was a randomised, active-controlled, Phase III trial investigating the efficacy of neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2+ metastatic breast cancer who had received two or more prior anti-HER2 based regimens in the metastatic setting. 621 patients were enrolled at 203 sites in 28 countries across Europe, North and South America, Asia, and Australia. The primary outcome measures for the trial were progression-free survival (PFS), and overall survival (OS). Median PFS was 5.6 months for patients who received N+C and 5.5 months for those receiving L+C (hazard ratio = 0.76, p = 0.0059). The PFS rate at 12 months was 29% versus 15%, respectively. Median OS was 21 months for patients receiving N+C, compared to 18.7 months for those receiving L+C (hazard ratio = 0.88, p = 0.2086). The most common adverse reactions of any grade (>5%) in the N+C arm were diarrhoea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, decreased weight, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms. About Specialised Therapeutics Founded in 2007, Specialised Therapeutics is the region's largest independent specialty pharmaceutical company, providing new therapies and technologies to patients in Australia, New Zealand and across Southeast Asia. Headquartered in Singapore, ST partners with global pharmaceutical, biotech and diagnostic companies to bring novel healthcare opportunities to patients who are impacted by a range of diseases. ST has built a strong track record of success, navigating complex regulatory, reimbursement and commercialisation environments in its diverse regions. The ST mission is to provide specialty therapies where there is an unmet need. The company's broad therapeutic portfolio currently includes novel agents in oncology, haematology, CNS, neurology, endocrinology, ophthalmology and supportive care, although it is not confined to these areas. ST is a member of the World Orphan Drug Alliance (WODA). Additional information can be found at . References: SOURCE Specialised Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Reduction in distant recurrence consistently deepened beyond 3-year Kisqali treatment duration in patients with node-positive (N+) and high-risk node-negative (N0) disease, as well as between anatomical stages1 Real-world 5-year distant recurrence data in high-risk patients with HR+/HER2- early breast cancer (EBC), regardless of nodal status, highlights importance of adding a CDK4/6 inhibitor to endocrine therapy for all eligible patients2 Late-breaking Kisqali data presentations at SABCS follow recent FDA and EMA approvals and recognition by NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®*) as only Category 1 preferred adjuvant treatment for both N+ and high-risk N0 disease in combination with AI3 EAST HANOVER, N.J., Dec. 10, 2024 /PRNewswire/ -- Novartis today announced results from an updated analysis of the pivotal Phase III NATALEE trial of Kisqali® (ribociclib) that underscore the extended efficacy beyond the duration of treatment in combination with endocrine therapy (ET). Results showed a sustained reduction in distant recurrence of 28.5% (HR=0.715; 95% CI 0.604-0.847; nominal P<0.0001), compared to ET alone, in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC)1. Reduction in distant recurrence, known as distant disease-free survival (DDFS), is a decrease in the rate of cancer returning and spreading to other organs. The DDFS with Kisqali was consistent across all pre-specified patient subgroups, including those with node-negative (N0) disease1. These late-breaking data are being presented at the 2024 San Antonio Breast Cancer Symposium (SABCS). "In day-to-day practice, we see a real and persistent risk of breast cancer coming back after early diagnosis, often as metastatic disease," said Paolo Tarantino, M.D., Advanced Fellow at Dana-Farber Cancer Institute and Harvard Medical School. "The latest NATALEE and real-world data presented at SABCS reaffirm we can better address risk of recurrence for all patients at high-risk, including selected patients with node-negative disease, by offering them adjuvant CDK4/6 inhibitor treatment in addition to endocrine therapy." DDFS results across pre-specified subgroups1,4** : Safety remains consistent with previous reports, and no new safety signals were identified5. Adverse events (AEs) of special interest (grade 3 or higher) were neutropenia (44.4%), liver-related AEs (e.g., elevated transaminases) (8.6%), and QT interval prolongation (1.0%)5. Real-World Risk of Distant Recurrence Further, real-world evidence presented at the meeting highlights the relatively high incidence of distant recurrences within 5 years despite ET monotherapy for patients at high-risk, regardless of nodal involvement2. "On the heels of its U.S. FDA and EMA approvals in early breast cancer, it is encouraging to see the continued benefit of adding Kisqali to standard endocrine therapy to help reduce the risk of recurrence," said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. "These data, together with the recent NCCN Guidelines® Category 1 preferred treatment recommendation for all eligible patients with early breast cancer, reinforce the opportunity to evolve adjuvant treatment to help a broader group of people." Additional research presented at the meeting further demonstrates the ongoing focus of Novartis to advance the care of people with breast cancer, including studies investigating the potential of radioligand therapies in the treatment of metastatic breast cancer (MBC)6. *NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. **The 4-year DDFS analysis was not prespecified and the trial was not powered to demonstrate statistical significance of these results. About NATALEE NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali with ET as an investigational adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO7,8. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable7,8. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria7,8. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial7,8. About Kisqali® (ribociclib) Kisqali® (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably. Kisqali has been approved as a treatment for breast cancer by regulatory authorities in 99 countries worldwide, including the U.S. FDA and the European Commission9,10. In the US, Kisqali is indicated in combination with an AI as an adjuvant treatment for adults with HR+/HER2- stage II and III early breast cancer at high risk of recurrence, as well as for the treatment of adults with HR+/HER2- advanced or MBC as initial ET; Kisqali is also approved in the metastatic indication in combination with fulvestrant as initial ET or following disease progression on ET in post-menopausal women or in men9. In EBC, ribociclib (Kisqali) is the only CDK4/6 inhibitor recommended by the NCCN Guidelines® for breast cancer for both all node-positive disease as well as for patients with no nodal involvement with high-risk disease characteristics, such as tumor size >5 cm, or for tumors sized 2-5 cm, either Grade 2 with high genomic risk/Ki-67 ≥20% or Grade 33. In MBC, Kisqali has consistently demonstrated statistically significant overall survival benefit across three Phase III trials11-21. The NCCN Guidelines® also recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of people living with HR+/HER2- when combined with an AI3, making Kisqali the preferred first-line treatment of choice for US prescribers in HR+/HER2- MBC. Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals. Please see full Prescribing Information for Kisqali, available at . About Novartis in Breast Cancer For more than 30 years, Novartis has been at the forefront of driving scientific advancements for people touched by breast cancer and improving clinical practice in collaboration with the global community. With one of the most comprehensive breast cancer portfolios and pipeline, Novartis leads the industry in discovery of new therapies and combinations in HR+/HER2- breast cancer, the most common form of the disease. Indication What is KISQALI? KISQALI® (ribociclib) is a prescription medicine used to treat adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer: in combination with an aromatase inhibitor for stage II and III early breast cancer with a high risk of coming back that has gotten worse or has spread to other parts of the body (advanced or metastatic breast cancer) in combination with: an aromatase inhibitor as the first endocrine-based therapy; or fulvestrant as the first endocrine-based therapy or following disease progression on endocrine therapy It is not known if KISQALI is safe and effective in children. IMPORTANT SAFETY INFORMATION KISQALI may cause serious side effects, including: Lung problems. KISQALI may cause severe or life-threatening inflammation of the lungs during treatment that may lead to death. Tell your health care provider right away if you have any new or worsening symptoms, including: trouble breathing or shortness of breath cough with or without mucus chest pain Severe skin reactions. Tell your health care provider or get medical help right away if you get severe rash or rash that keeps getting worse; reddened skin; flu-like symptoms; skin pain or burning, blistering of the lips, eyes, or mouth, blisters on the skin or skin peeling, with or without fever. Heart rhythm problems (QT prolongation). KISQALI can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. Your health care provider should check your heart and do blood tests before and during treatment with KISQALI Tell your health care provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you feel dizzy or faint Liver problems. KISQALI can cause serious liver problems. Your health care provider should do blood tests to check your liver before and during treatment with KISQALI. Tell your health care provider right away if you get any of the following signs and symptoms of liver problems: yellowing of your skin or the whites of your eyes (jaundice) dark or brown (tea-colored) urine feeling very tired loss of appetite pain on the upper right side of your stomach area (abdomen) bleeding or bruising more easily than normal Low white blood cell counts (neutropenia). Low white blood cell counts are very common during treatment with KISQALI and may result in infections that may be severe. Your health care provider should check your white blood cell counts before and during treatment with KISQALI. Tell your health care provider right away if you have signs and symptoms of low white blood cell counts or infections, such as fever and chills. Your health care provider may tell you to decrease your dose, temporarily stop, or completely stop taking KISQALI if you develop certain serious side effects during treatment with KISQALI. What should I tell my health care provider before taking KISQALI? Before you take KISQALI, tell your health care provider if you: have any heart problems, including heart failure, irregular heartbeats, and QT prolongation have ever had a heart attack have a slow heartbeat (bradycardia) have high blood pressure that is not controlled have decreased thyroid gland (hypothyroidism) have problems with the amount of potassium, calcium, phosphorus, or magnesium in your blood have fever, chills, or any other signs or symptoms of infection have liver problems have kidney problems are pregnant, or plan to become pregnant. KISQALI can harm your unborn baby If you are able to become pregnant, your health care provider should do a pregnancy test before you start treatment with KISQALI Females who are able to become pregnant and who take KISQALI should use effective birth control during treatment and for at least 3 weeks after the last dose of KISQALI Talk to your health care provider about birth control methods that may be right for you during this time If you become pregnant or think you are pregnant, tell your health care provider right away are breastfeeding or plan to breastfeed. It is not known if KISQALI passes into your breast milk. Do not breastfeed during treatment with KISQALI and for at least 3 weeks after the last dose of KISQALI Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. KISQALI and other medicines may affect each other, causing side effects. Know the medicines you take. Keep a list of them to show your health care provider or pharmacist when you get a new medicine. What should I avoid while taking KISQALI? Avoid eating grapefruit and avoid drinking grapefruit juice during treatment with KISQALI since these may increase the amount of KISQALI in your blood. The most common side effects of KISQALI in people with early breast cancer include: decreased white blood cell counts decreased red blood cell counts increased liver function tests infections increased kidney function test decreased platelet counts nausea headache tiredness The most common side effects of KISQALI in people with advanced or metastatic breast cancer include: decreased white blood cell counts decreased red blood cell counts increased liver function tests infections nausea increased kidney function test tiredness decreased platelet counts diarrhea vomiting headache constipation hair loss cough rash back pain low blood sugar level KISQALI may cause fertility problems in males, which may affect your ability to father a child. Talk to your health care provider if this is a concern for you. Tell your health care provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of KISQALI. For more information, ask your health care provider or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Please see accompanying full Prescribing Information including Patient Information . Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this media update, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this media update will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people's lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at and , and connect with us on LinkedIn, LinkedIn US, Facebook, X/Twitter, X/Twitter US and Instagram. References Hurvitz S et al. Distant disease-free survival (DDFS) across key subgroups from the phase 3 NATALEE trial of ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) in patients with HR+/HER2− early breast cancer (EBC). Presented at the San Antonio Breast Cancer Symposium, December 12, 2024. Texas, USA. Tarantino P et al. Risk of recurrence in real-world (RW) NATALEE- and monarchE-eligible populations of patients with HR+/HER2− early breast cancer (EBC) in an electronic health record (EHR)-derived database. Presented at the San Antonio Breast Cancer Symposium, December 11, 2024. Texas, USA. NCCN Guidelines. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) - Breast Cancer. Accessed December 2024. Hortobagyi G, Stroyakovskiy D, Yardley DA, et al. Ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) as adjuvant treatment in patients with HR+/HER2- early breast cancer: final invasive disease-free survival (iDFS) analysis from the NATALEE trial. Presented at San Antonio Breast Cancer Symposium (SABCS); December 8, 2023; San Antonio, USA. Fasching PA. Adjuvant Ribociclib (RIB) Plus Nonsteroidal Aromatase Inhibitor (NSAI) in Patients (Pts) With HR+/HER2− Early Breast Cancer (EBC): 4-Year Outcomes from the NATALEE Trial. LBA13. Proffered Paper presented at the European Society for Medical Oncology Congress, September 16, 2024. Barcelona, Spain. Campone M et al. Phase I/II study of the novel radioligand therapy [Lu]Lu-NeoB plus capecitabine in patients with ER+/HER2− advanced breast cancer (ABC) with GRPR expression after progression on prior endocrine therapy (ET) plus a CDK4/6 inhibitor (CDK4/6i) for ABC. Presented at the San Antonio Breast Cancer Symposium, December 12, 2024. Texas, USA. Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med. 2024;390(12):1080-1091. doi:10.1056/NEJMoa2305488 Clinicaltrials.gov. NCT03701334. A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/ HER2- Early Breast Cancer (NATALEE). Available from: . Accessed December 2024. Kisqali. Prescribing Information (US FDA). Novartis Pharmaceuticals Corporation; 2017. Accessed December 2024. Kisqali. Summary of product characteristics (SmPC). Novartis Europharm Limited; 2017. Accessed December 2024. Yardley DA et al. Pooled exploratory analysis of survival in patients (pts) with HR+/HER2- advanced breast cancer (ABC) and visceral metastases (mets) treated with ribociclib (RIB) + endocrine therapy (ET) in the MONALEESA (ML) trials. Poster presented at the European Society of Medical Oncology Congress. September 9-13, 2022. Paris, France. Neven P et al. Updated overall survival (OS) results from the first-line (1L) population in the Phase III MONALEESA-3 trial of postmenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL). Mini oral presented at the European Society for Medical Oncology Breast Cancer Congress. May 4, 2022. Paris, France. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663 Hortobagyi GN et al. Overall survival (OS) results from the phase III MONALEESA (ML)-2 trial of postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. LBA 17. Proffered paper presented at the European Society of Medical Oncology Congress, September 16-21, 2021. Lugano, Switzerland. Im SA, Lu YS, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381(4):307-316. doi:10.1056/NEJMoa1903765 Slamon DJ, Neven P, Chia S, et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020;382(6):514-524. doi:10.1056/NEJMoa1911149 Slamon DJ et al. Overall survival (OS) results of the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). LBA7_PR. Presented at the European Society of Medical Oncology Congress, September 29, 2019. Barcelona, Spain. Slamon DJ et al. Updated overall survival (OS) results from the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2− advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). Presented at the American Society of Clinical Oncology Annual Meeting, June 5, 2021. Chicago, USA. Tripathy D et al. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Presented at the San Antonio Breast Cancer Symposium, December 9, 2020. Texas, USA. Yardley D et al. Overall survival (OS) in patients (pts) with advanced breast cancer (ABC) with visceral metastases (mets), including those with liver mets, treated with ribociclib (RIB) plus endocrine therapy (ET) in the MONALEESA (ML) -3 and -7 trials. Presented at the American Society of Clinical Oncology Annual Meeting, June 2020. Chicago, USA. O'Shaughnessy J et al. Overall survival subgroup analysis by metastatic site from the Phase III MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with HR+/HER2− advanced breast cancer. Presented at the San Antonio Breast Cancer Symposium, December 7-10, 2021. Texas, USA. # # # Novartis Media Relations E-mail: [email protected] North America Michael Meo +1 862 274 5414 Novartis Investor Relations E-mail: [email protected] North America Sloan Simpson +1 862 345 4440 Jonathan Graham +1 201 602 9921 Parag Mahanti +1 973 876 4912 SOURCE Novartis Pharmaceuticals Corporation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics (“BBOT” or the “Company”), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, today announced the publication of preclinical data supporting the hypothesis that targeting both “ON” and “OFF” forms of KRAS G12C results in greater potency, deeper responses, and slowed development of resistance leading to significant benefits over “OFF” only KRAS G12C inhibitors approved in non-small cell lung cancer (NSCLC). The publication, titled “ Discovery of BBO-8520, a first-in-class direct and covalent dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRAS G12C ” was published in the peer-reviewed journal Cancer Discovery , a journal of the American Association for Cancer Research. Current KRAS G12C inhibitors work by binding to the inactive guanosine diphosphate (GDP)-bound “OFF” form of the protein, preventing its oncogenic activation. However, they do not directly target or inhibit the active guanosine triphosphate (GTP)-bound “ON” form. This limitation leaves KRAS G12C “ON” unaddressed, leading to adaptive resistance characterized by increased expression and activity of the active KRAS G12C “ON” state. The data in this manuscript demonstrate that BBO-8520, a first-in-class direct dual inhibitor, directly binds to both the “ON” and “OFF” states of KRAS G12C in the Switch-II/Helix3 pocket. There, it covalently modifies the target cysteine to disable effector binding to the “ON” state of KRAS G12C . In vivo , BBO-8520 demonstrates rapid target engagement and inhibition of downstream signaling, resulting in durable tumor regression in multiple tumor models, including those resistant to KRAS G12C “OFF” only inhibitors. “The aspiration to design a first-in-class, direct, dual inhibitor of the GTP-bound 'ON' and GDP-bound 'OFF' forms of KRAS G12C has been achieved,” said Pedro Beltran, PhD, Chief Scientific Officer of BBOT. “BBO-8520 is a dual inhibitor of KRAS G12C that provides optimal target coverage with exquisite potency, overcoming key deficiencies of 'OFF' only inhibitors, and represents a novel mechanism of action because it is the only direct inhibitor that actually blocks effector binding. Preclinical data shows that this novel mechanism delays the emergence of adaptive resistance seen with 'OFF' only inhibitors in the clinic. The potential of this approach holds significant promise for delivering enhanced clinical outcomes in patients with NSCLC.” “Using nuclear magnetic resonance (NMR) and X-ray crystallography, as well as biochemical and cell-based assays, we’ve been able to decipher the mechanism of action of this potent dual inhibitor,” said lead author Anna Maciag, PhD, Principal Scientist at Frederick National Laboratory for Cancer Research (FNLCR). “Our ability to apply the multitude of high throughput screens and assays available at FNLCR allowed for quick structure activity relationship (SAR) determination and progress.” Resistance to KRAS G12C “OFF” inhibitors primarily arises from increased KRAS G12C activity in its “ON” state. This can occur through mutant allele amplification or activation of receptor tyrosine kinases (RTKs) by growth factors. Newly synthesized KRAS is likely to bind GTP, as intracellular GTP concentrations are roughly ten times higher than GDP. As a result, upregulating the mutant protein’s transcription offers an efficient escape mechanism for cells to bypass the effects of “OFF” inhibitors. Similarly, receptor tyrosine kinase (RTK) activation can effectively overcome “OFF” only inhibitors by maintaining a high level of KRAS G12C in its “ON” state. This study shows that the presence of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) significantly impairs the potency of “OFF” inhibitors in vitro , while amplification of KRAS G12C is also detrimental in vivo . In contrast, BBO-8520 maintains exquisite potency in the presence of growth factors, mutant allele amplification, as well as when mutations are engineered to maintain KRAS G12C in the “ON” form. BBO-8520 is currently being evaluated in a Phase 1 study ( NCT06343402 ) of KRAS G12C NSCLC patients pre-treated with first generation KRAS G12C “OFF” inhibitors or with no prior KRAS G12C targeted therapy experience. The discovery of BBO-8520 was the result of a collaboration between the National Cancer Institute RAS Initiative at Frederick National Laboratory for Cancer Research, Lawrence Livermore National Laboratory, and BBOT. About TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics (BBOT) BridgeBio Oncology Therapeutics (BBOT) is a clinical-stage biopharmaceutical company advancing a next generation pipeline of novel small molecule therapeutics targeting RAS and PI3K malignancies. Initially formed as a subsidiary of BridgeBio, BBOT completed a $200M private financing with external investors in 2024 with the goal of improving outcomes for patients with cancers driven by the two most prevalent oncogenes in human tumors. For more information visit bridgebiooncology.com .