Trametinib dimethyl sulfoxide

Ad hoc announcement pursuant to Art. 53 LR First quarter Net sales declined -5% (cc 1 , -1% USD), as growth drivers were more than offset by US generic erosion Continued strong performance from priority brands including Kisqali (+55% cc), Pluvicto (+70% cc), Kesimpta (+26% cc), Scemblix (+79% cc) and Leqvio (+69% cc) Core operating income 1 down -14% (cc, -12% USD), due to lower net sales and higher R&D investment Core operating income margin 1 was 37.3% Operating income declined -11% (cc, -9% USD); net income down -13% (cc, -13% USD) Core EPS 1 declined -15% (cc, -13% USD) to USD 1.99 Free cash flow 1 was USD 3.3 billion , broadly in line with the prior-year quarter Q1 selected innovation milestones: Remibrutinib positive CHMP opinion for CSU, positive Phase III readout in CIndU and Phase II data in food allergy Ianalumab FDA Breakthrough Therapy designation and priority review in SjD Cosentyx FDA approval for pediatric HS patients, regulatory submissions for PMR Fabhalta positive Phase III eGFR results in IgAN, FDA priority review for traditional approval Completed acquisition of Avidity , adding three late-stage medicines addressing neuromuscular disease Full year 2026 guidance 2 reaffirmed Net sales expected to grow low single-digit and core operating income expected to decline low single-digit Basel, April 28, 2026 – Commenting on Q1 2026 results, Vas Narasimhan, CEO of Novartis, said: “Novartis delivered a strong start to 2026 across our priority brands and launches, while US generic erosion weighed on results in Q1 as expected. We continued to advance our pipeline, with compelling Phase III results for remibrutinib in chronic inducible urticaria and Phase II data in food allergy, reinforcing the medicine’s pipeline-in-a-pill potential. We also completed the acquisition of Avidity and announced early-stage deals to support our breast cancer and allergic disease franchises. With the momentum we are seeing across the business, we remain on track to deliver our full year guidance and look forward to multiple readouts in the second half that could raise our mid- to long-term growth outlook.” Key figures Q1 2026 Q1 2025 % change USD m 3 USD m 3 USD cc Net sales 13 113 13 233 -1 -5 Operating income 4 235 4 663 -9 -11 Net income 3 156 3 609 -13 -13 EPS (USD) 1.65 1.83 -10 -11 Free cash flow 3 330 3 391 -2 Core operating income 4 897 5 575 -12 -14 Core net income 3 794 4 482 -15 -17 Core EPS (USD) 1.99 2.28 -13 -15 1. Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 32 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year. 2. Please see detailed guidance assumptions on page 6. 3. USD millions unless indicated otherwise. Strategy Our focus Novartis is a “pure-play” innovative medicines company. We have a clear focus on four core therapeutic areas (cardiovascular-renal-metabolic, immunology, neuroscience and oncology), with multiple significant in-market and pipeline assets in each of these areas, that address high disease burden and have substantial growth potential. In addition to two established technology platforms (chemistry and biotherapeutics), three emerging platforms (gene & cell therapy, radioligand therapy and xRNA) are being prioritized for continued investment into new R&D capabilities and manufacturing scale. Geographically, we are focused on growing in our priority geographies – the US, China, Germany and Japan. Our priorities Accelerate growth : Renewed attention to deliver high-value medicines (NMEs) and focus on launch excellence, with a rich pipeline across our core therapeutic areas. Deliver returns : Continuing to embed operational excellence and deliver improved financials. Novartis remains disciplined and shareholder-focused in our approach to capital allocation, with substantial cash generation and a strong capital structure supporting continued flexibility. Strengthen foundations : Unleashing the power of our people, scaling data science and technology and continuing to build trust with society. Financials First quarter Net sales were USD 13.1 billion (-1%, -5% cc), with volume contributing 13 percentage points to growth, more than offset by 14 percentage points of generic competition. Pricing had a negative impact of 4 percentage points, including net 1 percentage point from revenue deduction adjustments in the US, and currency had a positive impact of 4 percentage points. Operating income was USD 4.2 billion (-9%, -11% cc), declining due to lower net sales and higher R&D investments, partly offset by higher divestment gains. Net income was USD 3.2 billion (-13%, -13% cc), mainly due to lower operating income. EPS was USD 1.65 (-10%, -11% cc), due to lower net income, partly offset by the benefit of the lower weighted average number of shares outstanding. Core operating income was USD 4.9 billion (-12%, -14% cc), declining due to lower net sales and higher R&D investments. Core operating income margin was 37.3% of net sales, decreasing 4.8 percentage points (4.1 percentage points in cc). Core net income was USD 3.8 billion (-15%, -17% cc), mainly due to lower core operating income. Core EPS was USD 1.99 (-13%, -15% cc), due to lower core net income, partly offset by the benefit of the lower weighted average number of shares outstanding. Free cash flow amounted to USD 3.3 billion, broadly in line with the prior-year quarter. Q1 priority brands Underpinning our financial results in the quarter is a continued focus on key growth drivers (ranked in order of contribution to Q1 growth) including: Kisqali (USD 1 516 million, +55% cc) sales grew strongly across all regions, with continued momentum in the early breast cancer indication as well as leadership in metastatic breast cancer. Pluvicto (USD 642 million, +70% cc) sales showed continued strong demand in the pre-taxane metastatic castration-resistant prostate cancer (mCRPC) setting in the US, as well as access expansion ex-US. Kesimpta (USD 1 164 million, +26% cc) sales grew across all regions, driven by increased demand and strong access. Leqvio (USD 452 million, +69% cc) accelerated growth ex-US, driven by strong uptake in China following NRDL-listing. Scemblix (USD 433 million, +79% cc) sales grew across all regions, with continued strong momentum from the early-line indication in the US, Japan and Germany. Fabhalta (USD 169 million, +103% cc) sales more than doubled in Q1, reflecting continued expansion in PNH and renal indications. R hapsido (USD 37 million) continued to show strong early uptake in the US, supported by a free drug program to facilitate patient access and increasing coverage. Cosentyx (USD 1 566 million, -2% cc) sales were broadly stable. US sales declined, as demand growth was offset by positive revenue deduction adjustments in the prior-year quarter. Ex-US, sales continued to grow. Underlying sales growth globally was +2% cc. Zolgensma Group (USD 302 million, -12% cc) sales declined, reflecting a lower incidence of SMA, despite continued strong share in the incident population, as well as treatment phasing. Net sales of the top 20 brands in the first quarter Q1 2026 % change USD m USD cc Cosentyx - excluding revenue deduction adjustments* 1 566 2 5 -2 2 Kisqali 1 516 59 55 Entresto 1 305 -42 -46 Kesimpta 1 164 29 26 Pluvicto 642 73 70 Jakavi 557 13 5 Tafinlar + Mekinist 493 -11 -14 Ilaris 475 13 10 Leqvio 452 76 69 Scemblix 433 82 79 Xolair 388 -15 -20 Zolgensma Group 302 -8 -12 Sandostatin Group 287 -9 -12 Lutathera 211 9 7 Exforge Group 203 13 7 Promacta/Revolade 184 -66 -68 Fabhalta 169 109 103 Tasigna 155 -59 -61 Diovan Group 150 0 -4 Myfortic 111 12 9 Top 20 brands total 10 763 1 -3 *Q1 sales growth impacted by US revenue deduction adjustments in the current and prior year. R&D update – key developments from the first quarter New approvals Cosentyx (secukinumab) FDA approved Cosentyx for the treatment of moderate to severe hidradenitis suppurativa (HS) in pediatric patients aged 12 years and older, making it the only IL‑17A inhibitor approved for this population. Regulatory updates Rhapsido (remibrutinib) EMA’s CHMP adopted a positive opinion recommending marketing authorization for remibrutinib as an oral treatment for chronic spontaneous urticaria (CSU) in adults with an inadequate response to H1‑antihistamine therapy. Ianalumab (VAY736) FDA granted Breakthrough Therapy designation and priority review to ianalumab for the treatment of Sjögren’s disease, following the first global Phase III trials to demonstrate a statistically significant reduction in disease activity. Regulatory submissions were completed for ianalumab in the US, Europe, China and Japan. Cosentyx (secukinumab) Regulatory submissions were completed for Cosentyx in polymyalgia rheumatica (PMR) in the US, Europe and Japan. Pluvicto (lutetium Lu177 vipivotide tetraxetan) Novartis withdrew its EMA type II variation application for Pluvicto to treat adult patients with PSMA+ mCRPC pre-chemotherapy, following CHMP feedback that they would not support the application. The withdrawal is not related to the quality, efficacy or safety of Pluvicto and does not impact ongoing clinical trials, approved indications or pending regulatory submissions inside or outside the EU. Importantly, the PSMAfore study, which supported the application, was the basis for the successful approval of Pluvicto in the pre-chemotherapy setting in the US, Japan and China. Pluvicto ’s value in this population is also reflected in evidence-based recommendations from leading professional guidelines, including ESMO, EAU, ASCO and NCCN Guidelines. Results from ongoing trials and other highlights Remibrutinib Positive topline results from the pivotal Phase III RemIND trial showed oral remibrutinib met its primary endpoint in chronic inducible urticaria (CIndU), achieving statistically significant and clinically meaningful complete response rates versus placebo at Week 12 across the three most prevalent CIndU types: symptomatic dermographism, cold urticaria and cholinergic urticaria. Remibrutinib was well tolerated and demonstrated a favorable safety profile, with no liver safety concerns reported. Based on these results, an sNDA for the treatment of symptomatic dermographism has been submitted to the FDA. Full data will be presented at an upcoming medical congress and submitted to health authorities globally. In a Phase II study in adults with IgE‑mediated peanut allergy, remibrutinib demonstrated superior efficacy versus placebo, with dose‑dependent effects and a rapid onset of action, and was well tolerated. Data were presented at the AAAAI Annual Meeting. A Phase III program in food allergy is on track to start in H2 2026. Fabhalta (iptacopan) In the Phase III APPLAUSE‑IgAN study, final two‑year results published in The New England Journal of Medicine showed that Fabhalta slowed kidney function decline by 49.3% versus placebo and reduced the risk of composite kidney failure events in adult patients with IgA nephropathy (IgAN). The safety pro consistent with previous findings. Fabhalta was granted priority review by FDA for traditional approval. Vanrafia (atrasentan) Final results from the Phase III ALIGN study showed a slowing in kidney function decline in IgAN patients treated with Vanrafia , with a positive difference in eGFR change from baseline vs. placebo at Week 136 (4 weeks after the end of study treatment, p = 0.057) and at Week 132 (at the end of treatment, nominal p = 0.039). Safety was consistent with previous findings. Novartis plans to submit these data for traditional approval in H1 2026. Pluvicto (lutetium Lu177 vipivotide tetraxetan) Real‑world analyses from the Novartis PRECISION platform showed that Pluvicto achieved a median progression‑free survival (PFS) of 13.5 months in men with PSMA+ mCRPC who were taxane‑naïve and had received at least one androgen receptor pathway inhibitor (ARPI). Longer median PFS was observed when Pluvicto was initiated after one prior ARPI compared with use after multiple ARPIs. Data were presented at the ASCO-GU Symposium. Cosentyx (secukinumab) In a matched adjusted indirect comparison analysis of efficacy and safety from Phase III trials in HS, including SUNSHINE and SUNRISE, Cosentyx showed greater flare prevention and a lower risk of Candida infections compared with bimekizumab through Week 48, while maintaining similar HiSCR50 responses. Data were presented at AAD. Del-zota One‑year data from the Phase I/II EXPLORE44 and EXPLORE44‑OLE studies evaluating del-zota in individuals with Duchenne muscular dystrophy amenable to exon 44 skipping (DMD44) showed sustained reductions in serum creatine kinase levels, significant increases in dystrophin, and improvements in multiple functional measures. Safety pro to date is consistent with earlier findings. Data were presented at MDA. Del-desiran Final results from the Phase I/II MARINA study of del-desiran in adults with myotonic dystrophy type 1 (DM1), published in The New England Journal of Medicine, showed effective delivery to muscle and a reduction in DMPK mRNA, and improvements across multiple functional measures. Safety pro to date is consistent with earlier findings. Del‑desiran is currently being evaluated in the Phase III HARBOR study in DM1, with readout anticipated in H2 2026. Selected transactions Novartis successfully completed the acquisition of Avidity Biosciences, strengthening its late-stage neuroscience pipeline and advancing its xRNA strategy. Novartis entered into an agreement with Synnovation Therapeutics to acquire SNV4818, a pan‑mutant selective PI3Kα inhibitor currently in Phase I/II for patients with HR+/HER2‑ breast cancer and other advanced solid tumors. The program aligns with Novartis’ strategy in breast cancer, and fits naturally alongside CDK inhibitors as well as endocrine (hormonal) therapies as part of a potential combination regimen. The transaction is expected to close in H1 2026, subject to customary closing conditions. Novartis entered into an agreement to acquire Excellergy, including Exl-111, a half-life extended, high-affinity anti-IgE antibody in Phase I, with a differentiated mechanism designed to dissociate receptor-bound IgE and drive faster and deeper FcεRIα downregulation. This acquisition builds on deep Novartis expertise in IgE biology and allergic disease, with the potential to offer earlier symptom relief, stronger disease control and more convenient dosing. The transaction is expected to close in H2 2026, subject to customary closing conditions. Capital structure and net debt Retaining a good balance between investment in the business, a strong capital structure, and attractive shareholder returns remains a priority. In Q1 2026, Novartis repurchased a total of 10.4 million shares for USD 1.6 billion on the SIX Swiss Exchange second trading line under the up-to USD 10 billion share buyback announced in July 2025 (with up to USD 6.1 billion still to be executed). In addition, 2.0 million shares (equity value of USD 0.3 billion) were repurchased from employees. In the same period, 12.3 million shares (equity value of USD 0.3 billion) were delivered to employees related to equity-based compensation plans. Novartis aims to offset the 2026 dilution related to equity-based compensation plans of employees over the remainder of the year, in addition to the share repurchases under the up-to USD 10 billion share buyback. Consequently, the total number of shares outstanding decreased by 0.1 million versus December 31, 2025. These treasury share transactions resulted in an equity decrease of USD 1.6 billion and a cash outflow of USD 1.9 billion. Net debt increased to USD 38.1 billion at March 31, 2026, compared to USD 21.9 billion at December 31, 2025. The increase was mainly due to the free cash flow of USD 3.3 billion being more than offset by the net cash outflow for M&A and intangible asset transactions of USD 12.5 billion, the USD 6.2 billion annual net dividend payment in March (which is the gross dividend of USD 9.1 billion reduced by the USD 2.9 billion Swiss withholding tax paid in April 2026, according to its due date), and cash outflows for treasury share transactions of USD 1.9 billion. As of Q1 2026, the long-term credit rating for the company is Aa3 with Moody’s Ratings and AA- with S&P Global Ratings. 2026 outlook Barring unforeseen events; growth vs. prior year in cc Net sales Expected to grow low single-digit Core operating income Expected to decline low single-digit Foreign exchange impact If late-April exchange rates prevail for the remainder of 2026, the foreign exchange impact for the year would be positive 2 percentage points on net sales and positive 1 percentage point on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website. Key figures 1 Q1 2026 Q1 2025 % change USD m 2 USD m 2 USD cc Net sales 13 113 13 233 -1 -5 Operating income 4 235 4 663 -9 -11 As a % of sales 32.3 35.2 Net income 3 156 3 609 -13 -13 EPS (USD) 1.65 1.83 -10 -11 Net cash flows from operating activities 3 676 3 645 1 Non-IFRS measures Free cash flow 3 330 3 391 -2 Core operating income 4 897 5 575 -12 -14 As a % of sales 37.3 42.1 Core net income 3 794 4 482 -15 -17 Core EPS (USD) 1.99 2.28 -13 -15 1. Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 32 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year. 2. USD millions unless indicated otherwise. Detailed financial results accompanying this press release are included in the Condensed Interim Financial Report at the link below: Disclaimer This communication contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995, that can generally be identified by words such as “expected,” “anticipated,” “can,” “will,” “continue,” “ongoing,” “growth,” “launch,” “expanded,” “deliver,” “accelerate,” “guidance,” “outlook,” “priority,” “potential,” “momentum,” “on track,” “look forward,” or similar expressions, or by express or implied discussions regarding: potential new products, potential new indications for existing products, potential product launches or potential future revenues from any such products; or results of ongoing clinical trials; potential future, pending or announced transactions; potential future sales or earnings; strategy, plans, expectations or intentions, including discussions regarding our continued investment into new R&D capabilities and manufacturing; our capital structure. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management 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 communication 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. Neither can there be any guarantee that the expected benefits or synergies from the transactions described in this communication will be achieved in the expected timeframe, or at all. In particular, our expectations could be affected by, among other things, uncertainties concerning: global healthcare cost containment, including ongoing government, payer and general public pricing and reimbursement pressures and requirements for increased pricing transparency; the success of key products, commercial priorities and strategy; the research and development of new products, including clinical trial results and additional analysis of existing clinical data; our ability to obtain or maintain proprietary intellectual property protection, including the ultimate extent of the impact on Novartis of the loss of patent protection and exclusivity on key products; our ability to realize the strategic benefits, operational efficiencies or opportunities expected from our external business opportunities; the development or adoption of new technologies, including artificial intelligence, and new business models; the implementation of our new IT projects and systems; potential significant breaches of information security or disruptions of our information technology systems; actual or potential legal proceedings, including regulatory actions or delays or government regulation related to the products and pipeline products described in this communication; safety, quality, data integrity, or manufacturing issues; our performance on and ability to comply with environmental, social and governance measures and requirements; major macroeconomic and geo- and socio-political developments, including the impact of any potential tariffs on our products or the impact of war in certain parts of the world; future global exchange rates; future demand for our products; and other risks and factors referred to in Novartis AG’s most recently filed Form 20-F and in subsequent reports filed with, or furnished to, the US Securities and Exchange Commission. Novartis is providing the information in this communication as of this date and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise. All product names appearing in italics are trademarks owned by or licensed to Novartis. 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 300 million people worldwide. Reimagine medicine with us: Visit us at and connect with us on LinkedIn , Facebook , X/Twitter and Instagram . Novartis will conduct a conference call with investors to discuss this news release today at 14:00 Central European time and 8:00 Eastern Time. A simultaneous webcast of the call for investors and other interested parties may be accessed by visiting the Novartis website. A replay will be available after the live webcast by visiting . Detailed financial results accompanying this press release are included in the Condensed Interim Financial Report at the link below. Additional information is provided on our business and pipeline of selected compounds in late-stage development. A copy of today's earnings call presentation can be found at . Important dates July 21, 2026 Second quarter & half year 2026 results October 27, 2026 Third quarter & nine months 2026 results November 18-19, 2026 Meet Novartis Management 2026 (London, UK) # # # Novartis Media Relations E-mail: media.relations@novartis.com Novartis Investor Relations Central investor relations line: +41 61 324 7944 E-mail: investor.relations@novartis.com Please find full media release in English attached and on the following link: Media Release (PDF) Further language versions are available through the following links: German version is available through the following link: Medienmitteilung (PDF)

ROCKVILLE, Md. and SUZHOU, China, April 19, 2026 (GLOBE NEWSWIRE) -- Ascentage Pharma Group International (NASDAQ: AAPG; HKEX: 6855), a global, commercial stage, integrated biopharmaceutical company engaged in the discovery, development and commercialization of novel, differentiated therapies to address unmet medical needs in cancer, announced that it will present four preclinical studies in poster format at the American Association for Cancer Research (AACR) 2026 Annual Meeting, held April 17 to 22, 2026 in San Diego, CA, USA. These posters feature three of the Company’s drug candidates, Olverembatinib (HQP1351), a novel BCR-ABL inhibitor; APG-2449, a FAK/ALK/ROS1 triple tyrosine kinase inhibitor; and APG-5918, a PRC2/EED inhibitor. Yifan Zhai, M.D., Ph.D., Chief Medical Officer of Ascentage Pharma , said, “These preclinical findings reflect our continued commitment to advancing innovative therapies across multiple cancer types. The four studies demonstrate the breadth and versatility of our pipeline, exploring the therapeutic potential of our key assets in combination with other approved treatment options in both hematologic malignancies and solid tumors. Notably, the research examines Olverembatinib’s potential beyond its approved use in China for chronic myeloid leukemia (CML), exploring new applications in areas such as endometrial carcinoma and mantle cell lymphoma, including combination approaches with BTK inhibitors. In addition, our evaluation of APG-2449 in BRAF-mutant tumors, and APG-5918 in small-cell lung cancer, underscores our strategic focus on addressing resistance mechanisms and exploring combination strategies. These preclinical investigations are designed to inform our clinical development strategies and complement our ongoing global registrational trials as we bring new treatment options to patients with significant unmet medical needs.” Detailed data presented at AACR 2026 Annual Meeting are summarized below: (Abstract #4583) Multitarget kinase inhibitor Olverembatinib (HQP1351) is efficacious and synergizes with chemotherapy in preclinical models of endometrial carcinoma (EC) Background: EC is the most common gynecologic malignancy in developed countries, with an incidence that is steadily increasing globally. Patients with advanced-stage, high-risk non-endometrioid EC subtypes or recurrent disease have a poor prognosis and limited treatment options. Olverembatinib is a tyrosine kinase inhibitor approved by the National Medical Products Administration (NMPA) of China for the treatment of patients with CML. It targets multiple kinases, including VEGFR1–3, FGFR1–4, Src family kinases, RAF, KIT, RET, and PDGFR. Drug sensitivity screening of 883 human cancer cell lines using the PRISM (Profiling Relative Inhibition Simultaneously in Mixtures) platform showed that EC is one of the tumor types most sensitive to Olverembatinib. This study further explored the antitumor effects of Olverembatinib alone or in combination with standard-of-care chemotherapy in preclinical EC models. Summary: In a broad range of preclinical in vitro and in vivo EC models, Olverembatinib was efficacious and synergized with chemotherapy agents to promote antitumor effects. Mechanistically, Olverembatinib combined with chemotherapy suppressed FGFR2, PI3K/AKT, and MEK/ERK signaling pathways, induced DNA damage, and resulted in enhanced cell apoptosis. These findings support future clinical evaluation of Olverembatinib and its combination with other approved treatment options in EC. (Abstract #5875) Multikinase inhibitor Olverembatinib (HQP1351) is efficacious and synergizes with BTK inhibitor acalabrutinib in mantle cell lymphoma (MCL) preclinical models Background: MCL is a rare, aggressive type of non-Hodgkin lymphoma. Although BTK inhibitors have transformed MCL treatment, response to monotherapy is limited, and efforts are underway to develop combination therapies. Olverembatinib, an investigational multikinase inhibitor (approved in China for CML), inhibits Src-family kinases (e.g., Lyn, Fyn, YES1) and BTK, which are essential for B-cell receptor (BCR) signaling and B-cell proliferation, differentiation, and activation. Hypothesizing that dual inhibition of Lyn and BTK pathways could enhance antitumor effects, this study evaluated Olverembatinib in combination with acalabrutinib in preclinical MCL models and explored potential mechanisms of action. Summary: Olverembatinib potently inhibited MCL cell proliferation both in vitro and in vivo and showed synergistic effects when combined with acalabrutinib. The combination significantly promoted apoptosis and induced G 0 /G 1 cell cycle arrest. Mechanistically, Olverembatinib inhibited phosphorylation of Lyn and its downstream BTK, while the combination further downregulated NF-kB activity. These data provide a scientific rationale for further clinical evaluation of this novel combination therapy in patients with MCL. (Abstract #1858) FAK inhibition by APG-2449 enhances the antitumor activity of MAPK pathway blockade in BRAF V600E-mutant tumor models Background: BRAF mutations occur in approximately 4% to 8% of all cancers, most frequently in colorectal cancer (CRC), melanoma, and non-small-cell lung cancer. The V600E mutation is the most common and functionally activating form, leading to constitutive activation of the mitogen activated protein kinase (MAPK) signaling cascade. Combined BRAF and MAPK kinase (MEK) inhibition has shown substantial clinical benefit in BRAF V600Emutant melanoma and CRC. However, resistance frequently develops through feedback reactivation of extracellular signal-regulated kinase (ERK) or compensatory activation of the phosphoinositide-3 kinase (PI3K)-AKT signaling pathway. Recent evidence indicates that focal adhesion kinase (FAK) signaling is also adaptively reactivated upon MAPK inhibition, contributing to therapeutic resistance. This study evaluated the effects of APG-2449, a potent and selective multi-kinase inhibitor that also targets FAK, on the antitumor activities of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib in BRAF V600E-mutant CRC and melanoma preclinical models. Summary: The results showed selective sensitivity of BRAF V600E-mutant cancer cell lines to APG-2449. APG-2449 suppresses compensatory signaling activation induced by MAPK pathway blockade and synergistically enhances the antitumor activity of dabrafenib + trametinib in preclinical models. These results warrant clinical development of APG-2449 for patients with melanoma or CRC harboring the BRAF V600E mutation. (Abstract #4500) Embryonic ectoderm development (EED) inhibitor APG-5918 synergizes with topoisomerase I inhibitors in preclinical small-cell lung cancer (SCLC) models through epigenetic priming of chemosensitivity Background: Although SCLC initially responds to platinum-based chemotherapy, it rapidly develops resistance, resulting in a poor prognosis. PRC2-mediated epigenetic silencing represses Schlafen 11 (SLFN11), a biomarker of sensitivity to DNA-damaging therapies, thereby contributing to treatment resistance. EZH2, the catalytic subunit of PRC2, promotes chemoresistance in part through SLFN11 repression. EED, another core PRC2 component, stabilizes the complex and maintains its methyltransferase activity, making it an attractive therapeutic target in SCLC. Topoisomerase I inhibitors, such as topotecan and irinotecan, are used in relapsed SCLC; however, their efficacy is limited when SLFN11 is epigenetically suppressed. APG-5918 is a selective and investigational EED inhibitor that disrupts PRC2 function. This study evaluated the antitumor activity of APG-5918 in combination with topoisomerase I inhibitors in preclinical SCLC models. Summary: In preclinical SCLC models, combination treatment with APG-5918 and topoisomerase I inhibitors synergistically inhibited cell proliferation and induced apoptosis. In vivo, APG-5918 combined with irinotecan demonstrated synergistic antitumor activity in the NCI-H446 SCLC cell-derived xenograft (CDX) model without significant body-weight loss, indicating favorable tolerability. Mechanistically, APG-5918 reduced the repressive histone mark H3K27me3, indicating on-target inhibition of PRC2 activity. Consistent with this effect, APG-5918 treatment increased SLFN11 and p21 expression. Notably, treatment with topotecan or SN-38 increased H3K27me3 levels, whereas APG-5918 reduced this effect. Combination treatment further decreased expression of PRC2 core components, suppressed cell-cycle progression, and enhanced DNA damage and apoptotic signaling, supporting a synergistic proapoptotic effect. The findings support clinical investigation of APG-5918 in combination with DNA-damaging agents as a promising therapeutic strategy for SCLC. *Olverembatinib, APG-2449, and APG-5918 are currently under investigation and have not been approved by the U.S. FDA. About Ascentage Pharma Ascentage Pharma Group International (NASDAQ: AAPG; HKEX: 6855) (“ Ascentage Pharma ” or the “ Company ”) is a global, commercial stage, integrated biopharmaceutical company engaged in the discovery, development and commercialization of novel, differentiated therapies to address unmet medical needs in cancer. The Company has built a rich pipeline of innovative drug products and candidates that include inhibitors targeting key proteins in the apoptotic pathway, such as Bcl-2 and MDM2-p53, next-generation kinase inhibitors, and protein degraders. The Company’s first approved product, Olverembatinib, is the first novel third-generation BCR-ABL1 inhibitor approved in China for the treatment of patients with CML in chronic phase (CML-CP) with T315I mutations, CML in accelerated phase (CML-AP) with T315I mutations, and CML-CP that is resistant or intolerant to first and second-generation TKIs. It is covered by the China National Reimbursement Drug List (NRDL). Ascentage Pharma is currently conducting an FDA-cleared global registrational Phase III trial, called POLARIS-2, of Olverembatinib for CML, as well as global registrational Phase III trials for patients with newly diagnosed Ph+ ALL, called POLARIS-1, and SDH-deficient GIST patients, called POLARIS-3. The Company’s second approved product, Lisaftoclax, is a novel Bcl-2 inhibitor for the treatment of various hematologic malignancies. Lisaftoclax has been approved by China’s National Medical Products Administration (NMPA) for the treatment of adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously received at least one systemic therapy including Bruton’s tyrosine kinase (BTK) inhibitors. The Company is currently conducting four global registrational Phase III trials: the FDA-cleared GLORA study of Lisaftoclax in combination with BTK inhibitors in patients with CLL/SLL previously treated with BTK inhibitors for more than 12 months with suboptimal response; the GLORA-2 study in patients with newly diagnosed CLL/SLL; the GLORA-3 study in newly diagnosed, elderly and unfit patients with AML; and the FDA-cleared GLORA-4 study in patients with newly diagnosed higher risk MDS. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies, such as Takeda, AstraZeneca, Merck, Pfizer, and Innovent, in addition to research and development relationships with leading research institutions, such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan. For more information, visit Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, contained in this press release may be forward-looking statements, including statements that express Ascentage Pharma’s opinions, expectations, beliefs, plans, objectives, assumptions or projections regarding future events or future results of operations or financial condition. These forward-looking statements are subject to a number of risks and uncertainties as discussed in Ascentage Pharma’s filings with the SEC, including those set forth in the sections titled “Risk factors” and “Cautionary note regarding forward-looking statements” in its Annual Report on Form 20-F for the year ended December 31, 2024, filed with the SEC on April 16, 2025, the sections headed “Forward-looking Statements” and “Risks Factors” in the prospectus of the Company for its Hong Kong initial public offering dated October 16, 2019, and other filings with the SEC and/or The Stock Exchange of Hong Kong Limited where the Company’s ordinary shares are listed it has made or it makes from time to time that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. The forward-looking statements contained in this presentation do not constitute profit forecast by the Company’s management. As a result of these factors, you should not rely on these forward-looking statements as predictions of future events. The forward-looking statements contained in this press release are based on Ascentage Pharma’s current expectations and beliefs concerning future developments and their potential effects and speak only as of the date of such statements. Ascentage Pharma does not undertake any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Contact Information Investor Relations: Stella Yang Ascentage Pharma Stella.Yang@ascentage.com +1 (301) 792-6286 Stephanie Carrington ICR Healthcare AscentageIR@icrhealthcare.com +1 (646) 277-1282 Media Relations: Sean Leous ICR Healthcare AscentagePR@icrhealthcare.com +1 (646) 866-4012