PSMA-Positive Castration-Resistant Prostatic Cancer

First Patient Dosed with CONV01-α in Phase II Clinical Trial in Patients with Metastatic Castration Resistant Prostate Cancer Drug Development Veteran Richard Messmann, MD Appointed as Chief Medical Officer to Lead the Development of CONV01-α Novo Holdings Invests $40 million in Series A Extension to Advance Clinical Development of Radiopharmaceuticals at Convergent Therapeutics CAMBRIDGE, Mass., Sept. 24, 2024 /PRNewswire/ -- Convergent Therapeutics Inc., a clinical stage biotechnology company focused on developing next generation radiopharmaceutical therapies for the treatment of prostate cancer and other cancers, today announced that the first patient has been dosed with CONV01-α in the Phase II CONVERGE-01 trial evaluating CONV01-α, Ac-225 rosopatamab tetraxetan, for the treatment of patients with prostate-specific membrane antigen (PSMA) PET-positive metastatic castration resistant prostate cancer (mCRPC). Previously conducted academic studies of CONV01-α have shown encouraging therapeutic results in patients with prostate cancer. According to Neil Bander, MD, Convergent's Co-founder and CSO, "In patients treated at Weill Cornell Medicine, CONV01-α demonstrated a prostate-specific antigen decline of 50% (PSA50) in 67% of patients and a PSA decline of 90% (PSA90) in 27% of patients." These results have prompted initiation of the CONVERGE-01 trial under Convergent's own Investigational New Drug License (IND). "We look forward to evaluating the full potential of CONV01-α and advancing the Phase II trial in the months ahead." The CONVERGE-01 trial is a Phase II, randomized, open-label, multicenter three-part study designed to assess the safety and efficacy of CONV01-α in patients with mCRPC. In Part 1, the first 5 participants will receive In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants will then be enrolled in either Part 2 (dose optimization) or Part 3 (dose escalation) depending on their prior treatment history. Part 2 will enroll Lu-177-PSMA-radioligand therapy-naïve participants and Part 3 will enroll participants who received prior Lu-177-PSMA-radioligand therapy. All patients will receive Ac-225 rosopatamab tetraxetan in a single fractionated two-week cycle. Further details of the trial can be found at under NCT identifier: NCT06549465. Chief Medical Officer Appointment Convergent announced that Richard Messmann, MD, MHS, MSc, has joined the company as Chief Medical Officer. Dr. Messmann is a medical oncologist and biochemist with over 25 years of experience in oncology drug development, including responsibility for the global clinical development and successful regulatory submission of Pluvicto® and Locametz® for the treatment of men with PSMA-expressing, mCRPC. Dr. Messmann has held leadership positions at Endocyte, Advanced Accelerator Applications (a subsidiary of Novartis), Fusion Pharmaceuticals, Amgen, Eli Lilly & Co., and others. Immediately prior to joining Convergent Therapeutics, Dr. Messmann was the Senior Vice President and clinical lead for Fusion's development of the actinium radiotherapeutic FPI-2265. While at Amgen, he was the executive medical director and global program lead for the development of xaluritamig (AMG 509) in prostate cancer. "We are excited to welcome Dr. Messmann to the Convergent team as we expand our clinical program for CONV01-α," said Convergent's Co-founder and CEO, Philip Kantoff, MD. "His deep knowledge and experience in oncology drug development, specifically leading the late-stage development of radiopharmaceuticals, is an important addition to our team as we look forward to progressing this asset forward." Series A Extension Funding Convergent announced a $40 million Series A extension by Novo Holdings, a holding and investment company wholly owned by the Novo Nordisk Foundation. This additional funding increases the total Series A raise to $130 million to support the development of Convergent's radiopharmaceutical pipeline, including CONV01-α. Jim Trenkle, PhD, Partner in the Venture Investments group at Novo Holdings, joins the Convergent Board of Directors. About CONV01-α CONV01-α, Convergent's alpha emitting radioantibody, combines the precision and pharmacokinetics of antibodies with the tumor-killing potential of alpha emitting radionuclides. Specifically, CONV01-α uses a humanized monoclonal antibody targeting prostate-specific membrane antigen (PSMA) which is highly overexpressed in prostate cancer cells. Since PSMA is a validated target, several therapeutics are directed at this antigen and CONV01-α is differentiated by its use of both an antibody and alpha emitter. CONV01-α is linked to a powerful radionuclide called 225Ac, which releases alpha particles which kill cancer cells through DNA double strand breaks. Unlike other radioactive sources, alpha particles deliver high-energy radiation over very short distances, thereby minimizing radiation exposure to healthy neighboring cells and tissues. Pairing highly selective antibodies with such a powerful yet precise payload offers the ideal combination to treat many types of cancers. About Convergent Therapeutics, Inc. Convergent Therapeutics Inc. is a clinical-stage biotechnology company focused on developing tumor-selective alpha radioantibodies to target cancer. The company was founded by world-renowned experts in clinical care and research, drug development and cancer biology and its proprietary platform is licensed from Cornell University. In harnessing the selectivity of antibodies and tumor-destructive potential of alpha radioisotopes, Convergent's radioantibodies precisely target cancer cells with potent, localized radiation. For more information, please visit and follow us on Twitter and LinkedIn. Media Relations: Bryan Blatstein Spectrum Science 917-714-2609 [email protected] SOURCE Convergent Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Crescendo Biologics presents preclinical data on lead clinical candidate CB307 and unveils its first ‘2 in 1’ immune cell engager CB699 at AACR 2024 Preclinical data demonstrate strong rationale for ongoing Phase 1b POTENTIA trial investigating conditional CD137 (4-1BB) agonist CB307 as monotherapy and in combination with pembrolizumab in patients with prostate cancer Simultaneous publication in prestigious Clinical Cancer Research journal, including research generated through successful collaboration with The Institute of Cancer Research, London Crescendo also debuts CB699, a mesothelin-directed, CD137 and CD40 dual agonist demonstrating tumour-targeted activation of T, NK, and B lymphocytes Cambridge, UK, 10 April 2024 – Crescendo Biologics Ltd (Crescendo), a clinical stage immuno-oncology company developing novel, targeted immune cell enhancing therapeutics, has presented preclinical data at the 2024 American Association for Cancer Research (AACR) Annual Meeting on its two leading programmes: Clinical programme CB307 a ‘1st and only’ in class CD137 (4-1BB) x PSMA bispecific for end-stage prostate cancer patientsFirst ‘2 in 1’ immune cell engager CB699, a mesothelin (MSLN) directed molecule designed to target both CD40 and CD137 These programmes are derived from Crescendo’s proprietary Humabody® VH platform which is associated with superior tumour penetration compared to traditional antibodies. Theodora Harold, CEO at Crescendo Biologics, commented: “Crescendo employs a tumour-targeted approach to directing immune cell activation against cancer. The data from our two lead programmes highlight the potential of immuno-oncology therapies that are potent and long-lasting, yet well-tolerated by patients. “The pharmacology data we have shared on CB307, underpins its clinical development in PSMA+ metastatic castration-resistant prostate cancer (mCRPC), which continues at pace in our ongoing Phase 1b trial. CB699 is a pipeline programme which has excited us with its potential and I am delighted that we have been able to share our early research at this year’s conference. These preclinical findings support this candidate’s progression into clinical development, and we look forward to providing further insights as the programme matures.” Abstract #5313: CB307: A dual targeting costimulatory Humabody® VH therapeutic for treating PSMA-positive tumoursThe functional activity of CB307, a first-in-class CD137 x PSMA bispecific Humabody®, designed to achieve a longer lasting anti-cancer effect whilst avoiding systemic toxicity, was assessed in preclinical models. The details of this research have also been published in Clinical Cancer Research, a journal of the AACR. The paper, ‘CB307: A dual targeting costimulatory Humabody® VH therapeutic for treating PSMA-positive tumours’, co-authored by Crescendo scientists and Regius Professor of Cancer Research, Johann de Bono from The Institute of Cancer Research, London, reports: CB307 demonstrated effective activation of both T and NK cells via the co-stimulatory receptor CD137 in a PSMA-dependent mannerIts combination with PD-(L)1 inhibitors showed supra-additive anti-tumour activity, which is retained even in absence of tumour PD-L1 expression, potentially enabling a wider patient population to benefit from checkpoint inhibitor therapiesAlthough prostate cancer has been considered an ‘immunologically cold’ tumour type, the data revealed co-localisation of CD137 and PSMA in metastatic prostate cancer lesions, supporting the use of CB307 in mCRPC Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, comments: “The data shared at AACR and published in Clinical Cancer Research support this novel candidate’s (CB307) clinical evaluation in PSMA+ mCRPC, both as a monotherapy and in combination settings.” Abstract #5302: CB699: A novel mesothelin-binding Humabody® CD40 and CD137 dual-agonist for enhancing immune cell responses against MSLN+ tumoursDerived from the Humabody® VH platform, CB699 is Crescendo’s first candidate in a novel class of tumour antigen-directed CD40 and CD137 dual agonists, designed to enhance the anti-tumour activity of multiple immune cell types. CB699 is a half-life extended CD40 x CD137 x MSLN trispecific molecule. The preclinical studies support Crescendo’s progression of the candidate towards clinical development: Pharmacokinetic data including preclinical dose range finding and half-life of CB699 support clinical development;The results demonstrated CB699’s ability to conditionally enhance both T cell and antigen-presenting cell (APC) signalling axes, providing a comprehensive anti-cancer immune response; andThe trispecific format was able to drive conditional CD40 agonism in the presence of either CD137+ or MSLN+ cells, and similarly, conditional CD137 agonism in the presence of either CD40+ or MSLN+ cells, potentially providing a potent yet safe way to target heterogeneous tumours Both abstracts are available on the AACR website and the posters are available on the Crescendo website under Posters & Publications. -Ends- For more information, please contact: Crescendo BiologicsTheodora Harold, CEO+44 (0) 12 2349 7140investors@crescendobiologics.commedia@crescendobiologics.comICR ConsiliumMary-Jane Elliott, David Daley, Sukaina Virji crescendo@consilium-comms.com About CB307CB307 is Crescendo’s lead clinical candidate, a first-in-class, half-life extended, CD137 x PSMA bispecific Humabody®, designed to deliver a safer and more durable anti-cancer response. CB307 conditionally activates only tumour-specific T cells, exclusively within the tumour microenvironment, using the CD137 co-stimulatory mechanism. Its unique format enables potent, tumour-specific killing, while avoiding systemic toxicity and can be applied to a broad range of PSMA+ cancer indications to address a large unmet medical need. Clinical development of CB307 is on track with the Phase 1b POTENTIA trial ongoing in adult patients with PSMA+ metastatic castration-resistant prostate cancer (mCRPC). POTENTIA (NCT04839991) is an open-label, dose escalation and cohort expansion study to assess the safety, tolerability and preliminary efficacy of CB307 as a monotherapy and in combination with pembrolizumab (KEYTRUDA®). About CB699CB699, a half-life extended CD40 x CD137 x mesothelin (MSLN) trispecific molecule, is the second candidate in Crescendo’s proprietary pipeline of novel, targeted immune-cell-enhancing therapeutics, derived from its Humabody® VH platform. CB699 aims at enhancing immune cell activity against MSLN+ tumours, using both immune cell and APC signalling axes. About Crescendo Biologics Crescendo Biologics is a private, clinical-stage immuno-oncology company developing novel, targeted immune cell-enhancing therapeutics derived from its proprietary Humabody® VH platform. Beyond Crescendo’s proprietary pipeline, the Company has global, multi-target discovery and development collaborations with Takeda and BioNTech, and an exclusive worldwide licensing agreement with Zai Lab. Located in Cambridge, UK, Crescendo is backed by blue-chip investors including Sofinnova Partners, Andera Partners, IP Group, BioNTech, Takeda, Quan Capital and Kreos Capital. Visit www.crescendobiologics.com and follow on LinkedIn and X (Twitter).

Ad hoc announcement pursuant to Art. 53 LR Transformation into a “pure-play” innovative medicines business is complete, with the spin-off of Sandoz; commentary below is on continuing operations2Q3 sales grew +12% (cc, +12% USD) with core operating income growing +21% (cc, +17% USD) Growth driven by continued strong performance from Kesimpta (+124% cc), Entresto (+31% cc), Kisqali (+76% cc), Pluvicto (+217% cc) and Scemblix (+157% cc) Q3 operating income grew +13% (cc, -4% USD) driven by higher sales and lower restructuring charges, partly offset by higher impairments through discontinuation of early stage development projects Q3 net income grew +37% (cc, +14% USD) mainly due to higher operating incomeQ3 free cash flow3 was USD 5.0 billion (+24% USD) driven by higher net cash flows from operating activitiesQ3 core EPS grew +29% (cc, +24% USD) to USD 1.74Strong nine months performance with sales growing +10% (cc, +8% USD) and core operating income growing +19% (cc, +13% USD)Q3 key innovation milestones, including positive Ph3 data for multiple pipeline assets with blockbuster potential: Cosentyx – FDA approval for intravenous formulation in three indications (PsA, AS, nr-axSpA)Demonstrated clinically meaningful and statistically significant Ph3 data for: 1) Pluvicto (mCRPC pre-taxane), 2) iptacopan (IgAN), 3) remibrutinib (CSU), 4) Lutathera (GEP-NETs) Kisqali – Ph3 NATALEE iDFS 500 event analysis complete; file submitted in EU, US submission planned for Q4 2023 Initiated previously announced, up-to USD 15 billion share buyback to be completed by year-end 2025Full-year 2023 guidance raised for core operating income based on strong momentum4 Net sales expected to grow high single digitCore operating income expected to grow mid to high teens (from low double digit to mid teens) Basel, October 24, 2023 – commenting on the quarter, Vas Narasimhan MD, CEO of Novartis, said: “Novartis delivered a very strong quarter, with double-digit sales and core operating income growth leading to a further upgrade to 2023 guidance. We have successfully executed the spin-off of Sandoz, allowing us to fully focus on high-value innovative medicines. Our growth drivers, including Kesimpta, Entresto, Kisqali and Pluvicto, continue to perform well in the market. Our robust pipeline also continues to deliver, and we have achieved important innovation milestones for Pluvicto, iptacopan, remibrutinib and Lutathera. We are confident in our mid-term growth outlook and remain committed to creating value for our shareholders.” Key figures1 Continuing operations2 Q3 2023 Q3 2022 % change 9M 2023 9M 2022 % change USD m USD m USD cc USD m USD m USD cc Net sales 11 782 10 492 12 12 34 017 31 630 8 10 Operating income 1 762 1 826 -4 13 7 187 6 191 16 31 Net income 1 513 1 330 14 37 5 934 4 734 25 41 EPS (USD) 0.73 0.61 20 45 2.84 2.16 31 49 Free cash flow 5 043 4 054 24 11 019 8 661 27 Core operating income 4 405 3 772 17 21 12 551 11 149 13 19 Core net income 3 585 3 035 18 23 10 320 8 983 15 22 Core EPS (USD) 1.74 1.40 24 29 4.95 4.09 21 28 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 48 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year. 2 As defined on page 37 of the Condensed Interim Financial Report, Continuing operations include the retained business activities of Novartis, comprising the Innovative Medicines Division and the continuing Corporate activities and Discontinued operations include operational results from the Sandoz business. 3 Effective January 1, 2023, Novartis revised its definition of free cash flow, to define free cash flow as net cash flows from operating activities less purchases of property, plant and equipment. To aid in comparability, the prior year free cash flow amounts have been revised to conform with the new free cash flow definition. See page 48 of the Condensed Interim Financial Report. 4 Please see detailed guidance assumptions on page 8. Strategy update Our focus Novartis has completed its transformation into a “pure-play” innovative medicines business, with the successful spin-off of Sandoz. Our focus is now centered on four core therapeutic areas (cardiovascular, renal and metabolic; immunology; neuroscience, and oncology). In each of these areas, we have multiple significant in-market and pipeline assets, all of which address diseases with a high 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. Financials Following the September 15, 2023, shareholders’ approval of the spin-off of the Sandoz business the Company reported its consolidated financial statements for the current and prior years as “continuing operations” and “discontinued operations.” Continuing operations include the retained business activities of Novartis, comprising the Innovative Medicines Division and the continuing corporate activities. Discontinued operations include the Sandoz Division and selected portions of corporate activities attributable to Sandoz’s business, as well as certain expenses related to the spin-off. With the spin-off of the Sandoz business, Novartis operates as a single global operating segment, being a focused innovative medicines company. The commentary below focuses on continuing operations. We also provide information on discontinued operations, which mainly includes Sandoz and allocated corporate activities. Continuing operations Third quarter Net sales were USD 11.8 billion (+12%, +12% cc) driven by volume growth of 17 percentage points. Pricing had a negative impact of 1 percentage point and generic competition had a negative impact of 4 percentage points. Operating income was USD 1.8 billion (-4%, +13% cc), mainly driven by higher sales and lower restructuring charges, partly offset by higher impairments through discontinuation of early stage development projects. Net income was USD 1.5 billion (+14%, +37% cc), mainly due to higher operating income and lower tax rate driven by non-recurring items. EPS was USD 0.73 (+20%, +45% cc), growing faster than net income, benefiting from lower weighted average number of shares outstanding. Core operating income was USD 4.4 billion (+17%, +21% cc), mainly driven by higher sales. Core operating income margin was 37.4% of net sales, increasing by 1.4 percentage points (+2.7 percentage points cc). Core net income was USD 3.6 billion (+18%, +23% cc), mainly due to higher core operating income. Core EPS was USD 1.74 (+24%, +29% cc), growing faster than core net income, benefiting from lower weighted average number of shares outstanding. Free cash flow amounted to USD 5.0 billion (+24% USD), compared with USD 4.1 billion in the prior year quarter driven by higher net cash flows from operating activities. Nine months Net sales were USD 34.0 billion (+8%, +10% cc) driven by volume growth of 16 percentage points. Pricing had a negative impact of 2 percentage points and generic competition had a negative impact of 4 percentage points. Operating income was USD 7.2 billion (+16%, +31% cc), mainly driven by higher sales, other income from legal matters, lower restructuring charges, partly offset by higher impairments through discontinuation of early stage development projects. Net income was USD 5.9 billion (+25%, +41% cc), mainly due to higher operating income. EPS was USD 2.84 (+31%, +49% cc), growing faster than net income, benefiting from lower weighted average number of shares outstanding. Core operating income was USD 12.6 billion (+13%, +19% cc), mainly driven by higher sales. Core operating income margin was 36.9% of net sales, increasing by 1.7 percentage points (+2.9 percentage points cc). Core net income was USD 10.3 billion (+15%, +22% cc), mainly due to higher core operating income. Core EPS was USD 4.95 (+21%, +28% cc), growing faster than core net income, benefiting from lower weighted average number of shares outstanding. Free cash flow amounted to USD 11.0 billion (+27% USD), compared with USD 8.7 billion in the prior year period driven by higher net cash flows from operating activities. Discontinued operations Results for discontinued operations in the third quarter and nine-months 2023 include the results of the Sandoz Division and selected portions of corporate activities attributable to Sandoz business, as well as certain expenses related to the spin-off. In connection with the Sandoz spin-off on October 4, 2023, the Company will report as part of its Q4 discontinued operations results a one-time non-cash non-taxable IFRS gain of approximately USD 5.9 billion. This IFRS gain represents mainly the excess amount of the IFRS distribution liability, which is the estimated fair value of the Sandoz business distributed to Novartis AG shareholders, over the then carrying value of Sandoz business net assets. Third quarter Discontinued operations net sales were USD 2.5 billion (+8%, +6% cc), mainly driven by ex-US growth. Operating loss amounted to USD 86 million, compared to an operating income of USD 342 million in the previous year. The operating loss in third quarter was driven by the discontinued corporate transaction cost related to spin-off of the Sandoz business, which were core adjustments. Core operating income was USD 250 million (-51%, -38% cc), mainly driven by lower gross margin and higher SG&A expenses. Net income from discontinued operations amounted to USD 250 million, compared to USD 245 million in the previous year. Nine months Discontinued operations net sales were USD 7.4 billion (+6%, +8% cc), mainly driven by ex-US growth. Operating income amounted to USD 265 million, compared to USD 1.1 billion in the previous year. The current year period includes the discontinued corporate transaction cost related to spin-off of the Sandoz business, which were core adjustments. Core operating income was USD 1.2 billion (-20%, -11% cc), mainly driven by higher SG&A expenses and R&D investments. Net income from discontinued operations amounted to USD 440 million, compared to USD 755 million in the previous year. Total company Third quarter Total company net income was USD 1.8 billion, mainly due to higher operating income and lower tax rate driven by non-recurring items compared to USD 1.6 billion in the prior year. EPS increased to USD 0.85 from USD 0.73 in prior year. Cash flows from operating activities amounted to USD 5.4 billion compared to USD 4.7 billion in the prior year. Free cash flow amounted to USD 5.0 billion compared to USD 4.4 billion in the prior year. Nine months Total company net income was USD 6.4 billion, mainly due to higher operating income compared to USD 5.5 billion in the prior year. EPS increased to USD 3.05 from USD 2.50 in prior year. Cash flows from operating activities amounted to USD 11.9 billion compared to USD 10.1 billion in the prior year. Free cash flow amounted to USD 11.0 billion compared to USD 9.3 billion in the prior year. Q3 key growth drivers Underpinning our financial results in the quarter is a continued focus on key growth drivers including: Kesimpta (USD 657 million, +124% cc) sales growth was driven by increased demand, strong access and benefitting from a one-time revenue deduction adjustment in Europe Entresto (USD 1 485 million, +31% cc) sustained robust demand-led growth, benefitting from the adoption of guideline-directed medical therapy across regions Kisqali (USD 562 million, +76% cc) sales grew strongly across all regions, based on increasing recognition of consistent overall survival and quality of life benefits Pluvicto (USD 256 million, +217% cc) continued sales growth in the US. Supply now unconstrained, focusing on initiating new patients Ilaris (USD 335 million, +24% cc) sales grew across all regions Scemblix (USD 106 million, +157% cc) sales grew across all regions, demonstrating the high unmet need in CML Leqvio (USD 90 million, +165% cc) launch in the US and other markets ongoing, with focus on patient on-boarding, removing access hurdles and enhancing medical education Cosentyx (USD 1 329 million, +4% cc) continued demand growth across key regions, partly offset by US revenue deduction fluctuations across periods. Ex-US sales grew +15% (cc) Promacta/Revolade (USD 576 million, +10% cc) grew across all regions, driven by increased use in chronic ITP and severe aplastic anemia Xolair (USD 369 million, +13% cc) sales grew across most regions Jakavi (USD 427 million, +9% cc) sales grew in Emerging Growth Markets, Europe and Japan, driven by strong demand in both myelofibrosis and polycythemia vera Tafinlar + Mekinist (USD 482 million, +8% cc) sales grew in the US and Emerging Growth Markets, driven by demand in BRAF+ adjuvant melanoma and NSCLC indications Lutathera (USD 159 million, +19% cc) sales grew mainly in the US, Japan and Europe due to increased demand Emerging Growth Markets* Overall, grew +17% (cc). Growth in China (+14% cc, USD 848 million) *All markets except the US, Canada, Western Europe, Japan, Australia, and New Zealand Net sales of the top 20 products in 2023 Q3 2023 % change 9M 2023 % change USD m USD cc USD m USD cc Entresto 1 485 31 31 4 400 31 33 Cosentyx 1 329 4 4 3 677 -1 1 Promacta/Revolade 576 10 10 1 706 10 12 Kesimpta- excl. revenue deduction adjust.* 657 12787 124 86 1 530 112 95 112 96 Kisqali 562 72 76 1 470 68 74 Tafinlar + Mekinist 482 7 8 1 436 10 13 Tasigna 464 -5 -5 1 402 -3 -1 Jakavi 427 11 9 1 276 9 11 Lucentis 363 -20 -22 1 174 -20 -19 Xolair 369 15 13 1 085 4 6 Sandostatin 338 15 15 998 7 8 Ilaris 335 23 24 979 18 20 Zolgensma 308 -3 -2 928 -13 -11 Gilenya 270 -47 -48 771 -54 -53 Pluvicto 256 220 217 707 nm nm Exforge Group 187 1 3 557 -5 -1 Galvus Group 181 -15 -4 539 -17 -10 Diovan Group 153 -4 -1 466 -9 -4 Lutathera 159 20 19 458 34 34 Gleevec/Glivec 144 -19 -17 433 -24 -21 Top 20 brands total 9 045 13 13 25 992 9 11 nm= not meaningful* Sales growth benefiting from a one-time revenue deduction adjustment in Europe R&D update - key developments from the third quarter New approvals Leqvio Approved in China and Japan as the first and only small interfering RNA (siRNA) therapy for LDL-C reduction Cosentyx In October, FDA approved the intravenous formulation in three indications: Psoriatic Arthritis, Ankylosing Spondylitis, and non-radiographic axial SpA Regulatory updates Kisqali EU file submission in adjuvant early breast cancer setting; US submission planned for Q4 2023 Adakveo EC adopts decision endorsing CHMP recommendation to revoke conditional marketing authorization Results from ongoing trials and other highlights iptacopan In October, Ph3 APPLAUSE-IgAN study interim analysis demonstrated clinically meaningful and highly statistically significant proteinuria reduction in patients with IgA nephropathy. The trial met its pre-specified interim analysis (9 months) primary endpoint, demonstrating superiority vs. placebo in proteinuria reduction, with safety consistent with previously reported data. Novartis plans to review interim data with regulatory authorities for accelerated approval; study continues with final readout at 24 months remibrutinib Ph3 REMIX-1 and REMIX-2 studies met all primary and secondary endpoints, showing fast, clinically meaningful improvements across urticaria disease activity scores. Remibrutinib demonstrated a favorable safety profile with rates of adverse events comparable to placebo and balanced liver function tests across both studies.Final (52 weeks) readout and submissions to health authorities are expected in 2024. Full data will be presented at upcoming medical meetings Pluvicto Ph3 PSMAfore study demonstrated clinically meaningful and statistically significant rPFS benefit in patients with PSMA+ mCRPC in the pre-taxane setting. Per updated analysis presented at ESMO, median rPFS more than doubled compared to ARPI switch. Patients on Pluvicto showed improved quality of life compared to daily oral ARPI, along with improvements in other clinically meaningful efficacy endpoints including PSA response, ORR, DOR and time to symptomatic skeletal event, with favorable safety. Pre-specified crossover-adjusted OS analysis demonstrated a HR of 0.80 (0.48, 1.33); the unadjusted ITT OS analysis was confounded by a high rate of crossover. Novartis is continuing to collect OS data, regulatory filings are anticipated in 2024 Lutathera Ph3 NETTER-2 study demonstrated clinically meaningful and statistically significant improvement in PFS (primary endpoint) in patients with newly diagnosed somatostatin receptor (SSTR)-positive, Grade 2 and 3, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) vs. high-dose long-acting octreotide alone. The trial also met its key secondary endpoint of ORR. No new or unexpected safety findings were observed and data are consistent with the already well-established safety profile of Lutathera.Data to be presented at an upcoming medical meeting and discussed with regulatory authorities, with submissions to follow Kisqali Ph3 NATALEE iDFS 500 event analysis complete. Updated data is consistent with the interim analysis results announced in March 2023 and will be communicated at an upcoming medical meeting.Health-related quality of life (HRQoL) analyses from Ph3 NATALEE trial demonstrated that patients with early breast cancer receiving adjuvant Kisqali plus ET for up to 3 years maintained physical and social functioning; psychological well-being; and overall health scores, compared to baseline. Data was presented at the ESMO Virtual Plenary 2023 Leqvio Long-term data from Ph3 ORION-8 demonstrated that Leqvio, in addition to statin therapy, provides consistent low-density lipoprotein cholesterol (LDL-C) reduction beyond six years of treatment in patients with atherosclerotic cardiovascular disease (ASCVD), increased risk of ASCVD or heterozygous familial hypercholesterolemia. Efficacy and safety were consistent with previously reported Ph3 results. Data was presented at ESC 2023 GT005 (PPY988) Development in Geographic Atrophy secondary to dry-Age-related Macular Degeneration discontinued based on benefit-risk assessment. No new safety signals identified. Patients treated will be provided with long term safety follow up Tislelizumab Novartis and BeiGene mutually agreed to terminate the collaboration and license agreement for tislelizumab for certain markets. With the termination, BeiGene will re-assume all development and commercialization rights for tislelizumab, and Novartis will manufacture tislelizumab for certain markets. BeiGene will also provide Novartis with ongoing clinical supply of tislelizumab to support its clinical trials ‘Front of Eye’ Assets Divestment completed of ‘front of eye’ ophthalmology assets to Bausch + Lomb 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. During the first nine months of 2023, Novartis repurchased a total of 74.9 million shares for USD 7.2 billion on the SIX Swiss Exchange second trading line. These repurchases included 52.8 million shares (USD 4.9 billion) under the USD 15 billion share buyback (announced in December 2021 and completed in June 2023) and 10.4 million shares (USD 1.1 billion) under the new up-to USD 15 billion share buyback announced in July 2023. In addition, 11.7 million shares (USD 1.2 billion) were repurchased to mitigate dilution related to participation plans of associates. Furthermore, 1.4 million shares (for an equity value of USD 0.1 billion) were repurchased from associates. In the same period, 12.2 million shares (for an equity value of USD 0.8 billion) were delivered as a result of options exercised and share deliveries related to participation plans of associates. Consequently, the total number of shares outstanding decreased by 64.1 million versus December 31, 2022. These treasury share transactions resulted in an equity decrease of USD 6.5 billion and a net cash outflow of USD 7.3 billion. As of September 30, 2023, net debt excluding net debt related to discontinued operations increased to USD 10.8 billion compared to USD 7.2 billion total net debt at December 31, 2022. The increase was mainly due to the USD 7.3 billion annual dividend payment, net cash outflow for treasury share transactions of USD 7.3 billion and net M&A / intangible assets transactions of USD 2.9 billion. This increase in net debt was partially offset by USD 11.0 billion free cash flow. As part of the spin-off, Sandoz incurred total bank debt of approximately USD 3.7 billion and paid approximately USD 3.0 billion in cash, including payment in satisfaction of certain intercompany indebtedness owed by Sandoz and its subsidiaries to Novartis and its affiliates as of September 30, 2023. This reduced the net debt position of Novartis by USD 3.0 billion. As of Q3 2023, the long-term credit rating for the company is A1 with Moody’s Investors Service and AA- with S&P Global Ratings. 2023 outlook raised due to strong momentum Barring unforeseen events; growth vs prior year in cc Previous Guidance Net sales Expected to grow high single digit Unchanged Core operating income Expected to grow mid to high teens (from low double digit to mid teens) Key assumptions: No US Entresto Gx at risk launch in 2023No Sandostatin LAR generics enter in the US in 2023 Entresto patent update Novartis has appealed to reverse the negative US District Court decision and to uphold the validity of its combination patent covering Entresto and other combinations of sacubitril and valsartan, which expires in 2025 (with pediatric exclusivity). No generics have tentative or final approval in the US. Any US commercial launch of a generic Entresto product prior to the final outcome of Novartis combination patent appeal, or ongoing litigations involving other patents, may be at risk of later litigation developments. Foreign exchange impactIf late-October exchange rates prevail for the remainder of 2023, the foreign exchange impact for the year would be negative 2 percentage point on net sales and negative 6 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website. Key figures1 Continuing operations2 Q3 2023 Q3 2022 % change 9M 2023 9M 2022 % change USD m USD m USD cc USD m USD m USD cc Net sales 11 782 10 492 12 12 Net sales 34 017 31 630 8 10 Operating income 1 762 1 826 -4 13 Operating income 7 187 6 191 16 31 As a % of sales 15.0 17.4 As a % of sales 21.1 19.6 Net income 1 513 1 330 14 37 Net income 5 934 4 734 25 41 EPS (USD) 0.73 0.61 20 45 EPS (USD) 2.84 2.16 31 49 Cash flows from operating activities 5 304 4 275 24 Cash flows from operating activities 11 673 9 271 26 Non-IFRS measures Non-IFRS measures Free cash flow 5 043 4 054 24 Free cash flow 11 019 8 661 27 Core operating income 4 405 3 772 17 21 Core operating income 12 551 11 149 13 19 As a % of sales 37.4 36.0 As a % of sales 36.9 35.2 Core net income 3 585 3 035 18 23 Core net income 10 320 8 983 15 22 Core EPS (USD) 1.74 1.40 24 29 Core EPS (USD) 4.95 4.09 21 28 Discontinued operations2 Q3 2023 Q3 2022 % change 9M 2023 9M 2022 % change USD m USD m USD cc USD m USD m USD cc Net sales 2 476 2 286 8 6 Net sales 7 428 6 998 6 8 Operating (loss)/income -86 342 nm nm Operating income 265 1 057 -75 -60 As a % of sales nm 15.0 As a % of sales 3.6 15.1 Net income 250 245 2 79 Net income 440 755 -42 -18 Non-IFRS measures Non-IFRS measures Core operating income 250 510 -51 -38 Core operating income 1 185 1 486 -20 -11 As a % of sales 10.1 22.3 As a % of sales 16.0 21.2 Total company Q3 2023 Q3 2022 % change 9M 2023 9M 2022 % change USD m USD m USD cc USD m USD m USD cc Net income 1 763 1 575 12 44 Net income 6 374 5 489 16 33 EPS (USD) 0.85 0.73 16 51 EPS (USD) 3.05 2.50 22 40 Cash flows from operating activities 5 378 4 721 14 Cash flows from operating activities 11 911 10 125 18 Non-IFRS measures Non-IFRS measures Free cash flow 5 043 4 435 14 Free cash flow 11 038 9 325 18 Core net income 3 784 3 419 11 16 Core net income 11 209 10 101 11 18 Core EPS (USD) 1.83 1.58 16 22 Core EPS (USD) 5.37 4.60 17 24 nm= not meaningful 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 48 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.2 As defined on page 37 of the Condensed Interim Financial Report, Continuing operations include the retained business activities of Novartis, comprising the Innovative Medicines Division and the continuing Corporate activities and Discontinued operations include operational results from the Sandoz business. Detailed financial results accompanying this press release are included in the Condensed Interim Financial Report at the link below:https://ml-eu.globenewswire.com/resource/download/1a97fd38-edbc-49ea-9350-8042dc006c1c/ Disclaimer This press release 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 “guidance,” “expected,” “momentum,” “continue,” “drivers,” “confident,” “outlook,” “remain,” “committed,” “prioritized,” “prioritizing,” “continued,” “growing,” “growth,” “plans,” “on-track,” “continuing,” “anticipated,” “to follow,” “will,” “outlook,” “may,” “upcoming,” “ongoing,” “focus,” “pipeline,” “potential,” “estimated,” “launch,” “to deliver,” “transformation,” “transformative,” “address,” “planned,” “focusing,” “accelerated,” “long-term,” “innovation,” “priority,” “can,” “awaiting,” or similar expressions, or by express or implied discussions regarding potential new products, potential new indications for existing products, potential product launches, or regarding potential future revenues from any such products; or regarding potential future, pending or announced transactions; or regarding potential future sales or earnings of Novartis; or regarding discussions of strategy, priorities, plans, expectations or intentions, including our transformation into a “pure-play” innovative medicines business; or regarding our liquidity or cash flow positions and our ability to meet our ongoing financial obligations and operational needs; or regarding our USD 15 billion share buyback; or regarding our appeal of the negative decision of the US District Court for the District of Delaware on the validity of our patent covering Entresto and combinations of sacubitril and valsartan. 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. You should not place undue reliance on these statements. There can be no guarantee that the investigational or approved products described in this press release 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 expected benefits or synergies from the transactions described in this press release will be achieved in the expected timeframe, or at all. In particular, our expectations could be affected by, among other things: liquidity or cash flow disruptions affecting our ability to meet our ongoing financial obligations and to support our ongoing business activities; the impact of a partial or complete failure of the return to normal global healthcare systems including prescription dynamics; global trends toward healthcare cost containment, including ongoing government, payer and general public pricing and reimbursement pressures and requirements for increased pricing transparency; uncertainties regarding potential significant breaches of data security or data privacy, or disruptions of our information technology systems; regulatory actions or delays or government regulation generally, including potential regulatory actions or delays with respect to the development of the products described in this press release; the potential that the benefits and opportunities expected from our planned spin-off of Sandoz may not be realized or may be more difficult or take longer to realize than expected; the uncertainties in the research and development of new healthcare 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; safety, quality, data integrity, or manufacturing issues; uncertainties involved in the development or adoption of potentially transformational technologies and business models; uncertainties regarding actual or potential legal proceedings, investigations or disputes; our performance on environmental, social and governance measures; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; uncertainties regarding future global exchange rates; uncertainties regarding future demand for our products; 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 press release 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 AG and its subsidiaries. BAUSCH + LOMB is a registered trademark of Bausch & Lomb Incorporated. About Novartis Novartis is a focused 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 https://www.novartis.com 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 https://www.novartis.com/investors/event-calendar. Detailed financial results accompanying this press release are included in the condensed interim financial report at the link below. Additional information is provided on Novartis divisions and pipeline of selected compounds in late stage development and a copy of today's earnings call presentation can be found at https://www.novartis.com/investors/event-calendar. Important dates November 13, 2023 Impact and Health Equity Annual Event November 28, 2023 R&D Day Please find full media release in English attached and on the following link: Media release (PDF) German version is available through the following link: Medienmitteilung (PDF) French version is available through the following link: Communiqué aux médias (PDF)