On January 30, 2025 Tubulis reported that its second drug candidate, TUB-030, has entered clinical evaluation with successful dosing of the first patient in the 5-STAR 1-01 Phase I/IIa trial (NCT06657222). The study is evaluating TUB-030, Tubulis’ next-generation antibody-drug conjugate (ADC), in patients with advanced solid tumors (Press release, Tubulis, JAN 30, 2025, View Source [SID1234649970]). The ADC targets 5T4, an oncofetal antigen expressed in a broad range of solid tumors. The program was developed using Tubulis’ proprietary Tubutecan linker-payload platform, which enables superior biophysical properties for precise and sustained on-tumor payload delivery.

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"This milestone for TUB-030 demonstrates our ability to execute on our strategy to advance innovative programs into our proprietary pipeline and rapidly bring them into the clinic," said Dominik Schumacher, PhD, Chief Executive Officer and Co-founder of Tubulis. "As an organization, Tubulis has made a large step forward with two differentiated ADC molecules in clinical evaluation in less than a year. Our goal is to continue being an innovation driver in the field by delivering on the transformative potential of our platforms for patients."

The multicenter, first-in-human, dose escalation and optimization Phase I/IIa study 5-STAR 1-01 aims to investigate the safety, tolerability, pharmacokinetics, and efficacy of TUB-030 as a monotherapy to treat a broad range of solid tumors. The trial will enroll a total of 130 patients and will be conducted at sites across the US and Canada. Phase I comprises dose escalation to determine the safety profile and to identify the maximum tolerated dose and/or the identified dose for optimization in patients with advanced solid tumor indications. Phase IIa will focus on dose optimization, safety, and preliminary efficacy of TUB-030 in selected indications.

"Building on our strong preclinical efficacy and safety data, we are expecting that targeting 5T4 with our high-performance ADC technology may offer a new precision therapy option for a variety of solid tumor indications. With our differentiated target, a strong bystander effect and efficient and durable target engagement via the Tubutecan platform, TUB-030 provides the potential to induce robust anti-tumor activity in 5T4-expressing tumors," stated Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer at Tubulis.

TUB-030 consists of a humanized, Fc-silenced IgG1 antibody targeting 5T4 equipped with Tubulis’ proprietary Tubutecan technology, which is based on P5 conjugation chemistry and the topoisomerase-1 inhibitor exatecan. Tubulis previously presented a comprehensive preclinical data set at AACR (Free AACR Whitepaper) demonstrating TUB-030’s stability and minimal loss of linker-payload conjugation. In a range of preclinical models, TUB-030 produced high and long-lasting anti-tumor responses, including responses at relatively low 5T4 expression levels, while maintaining an excellent safety and tolerability profile. A single treatment with TUB-030 eliminated tumors in a triple-negative breast cancer mouse model, further underlining its potential efficacy. Preclinical analysis including safety, efficacy and pharmacokinetics demonstrated that TUB-030 has a therapeutic window in a large variety of solid tumors.

About TUB-030 and the Tubutecan Technology

Tubulis’ second antibody-drug conjugate (ADC) TUB-030 is directed against 5T4, an oncofetal antigen, expressed in a broad range of solid tumor types. It consists of an IgG1 antibody targeting 5T4 connected to the Topoisomerase I inhibitor exatecan through a cleavable linker system based on the company’s proprietary P5 conjugation technology with a homogeneous DAR of 8. P5 conjugation is a novel chemistry for cysteine-selective conjugation that enables ADC generation with unprecedented linker stability and biophysical properties. The candidate is currently being investigated in a multicenter Phase I/IIa study (5-STAR 1-01, NCT06657222) that aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-030 as a monotherapy in advanced solid tumors.

On January 30, 2025 enGene Holdings Inc. (Nasdaq: ENGN, or "enGene" or the "Company"), a clinical-stage genetic medicines company whose non-viral lead investigational product detalimogene voraplasmid (also known as detalimogene, and previously EG-70) is in an ongoing pivotal study in patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), reported three poster presentations at the 2025 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) to be held February 13-15, 2025 in San Francisco (Press release, enGene, JAN 30, 2025, View Source [SID1234649969]).

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"Patients with NMIBC often face a debilitating, multi-year journey with limited treatment options and significant negative impacts to daily life. These patients are most commonly treated by community urologists who face unique challenges accessing and providing optimal care, including global treatment shortages and complex usage and handling," said Ron Cooper, Chief Executive Officer of enGene. "We are determined to develop genetic therapies for underserved conditions like NMIBC and ultimately provide a long overdue treatment innovation designed to advance care and ease the treatment burden."

There are an estimated 730,000 patients in the U.S. living with bladder cancer, and approximately 75% to 80% of all bladder cancer diagnoses are NMIBC. Among patients diagnosed with high-risk NMIBC, more than half (50-70%) will become BCG-unresponsive and experience recurrence and/or progression after treatment.

"The current treatment options for patients with high-risk NMIBC are sadly sub-optimal, often resulting in disease progression, recurrence or removal of the bladder as a life-altering measure of last resort," said Anthony Cheung, Chief Scientific Officer and Co-Founder of enGene. "If approved, we believe detalimogene voraplasmid will be uniquely compelling to both patients and physicians by combining a streamlined administration process designed to ease the treatment experience with durable efficacy and a favorable safety and tolerability profile."

Presentation details are outlined below:

Preliminary results from LEGEND: A phase 2 study of detalimogene voraplasmid (EG-70), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)

Abstract #: 802
Poster #: F29
Clinical Trial Registration Number: NCT04752722
Session Title: Poster Session B: Urothelial Carcinoma
Presentation Date/Time: Friday, February 14 from 11:30am-12:45pm PT
Location: Level 1, West Hall
Presenting Author: John Taylor III, MD, MS, Professor of Urology & Cancer Biology, University of Kansas Cancer Center
Mechanism of action and translation to the clinic of detalimogene voraplasmid (EG-70): A novel, investigational, non-viral immunotherapy for non-muscle-invasive bladder cancer (NMIBC)

Abstract #: 826
Poster #: G22
Clinical Trial Registration Number: NCT04752722
Session Title: Poster Session B: Urothelial Carcinoma
Presentation Date/Time: Friday, February 14 from 11:30am-12:45pm PT
Location: Level 1, West Hall
Presenting Author: Vikram Narayan, MD, Assistant Professor in the Department of Urology at Emory University School of Medicine
A phase 1/2 study of detalimogene voraplasmid (EG-70) intravesical monotherapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC)

Abstract #: TPS886
Poster #: J14
Clinical Trial Registration Number: NCT04752722
Session Title: Trials In Progress Poster Session B: Urothelial Carcinoma
Presentation Date/Time: Friday, February 14 from 11:30am-12:45pm PT
Location: Level 1, West Hall
Presenter: Shreyas Joshi, MD, MPH, Assistant Professor in the Department of Urology at Emory University School of Medicine
About Non-Muscle Invasive Bladder Cancer (NMIBC)

Non-muscle invasive bladder cancer (NMIBC) is a disease with a significant patient burden, high clinical needs and massive economic impact on our healthcare system. NMIBC occurs when cancer cells grow in the tissues that line the interior of the bladder, but the cancer has not yet penetrated deeper into the muscle of the bladder wall. About 75-80% of new bladder cancer diagnoses are NMIBC. Patients suffering from high-risk NMIBC who are unresponsive to the standard of care, Bacillus Calmette-Guérin (BCG), face high rates of disease recurrence (50-70%) and are subject to full removal of the bladder (cystectomy) as a curative but life-altering next step.

About Detalimogene Voraplasmid

Detalimogene voraplasmid (formerly known as EG-70) is a novel, investigational, non-viral genetic medicine for patients with high-risk, non-muscle invasive bladder cancer (NMIBC), including Bacillus Calmette-Guérin (BCG)-unresponsive disease. It is designed to be instilled in the bladder and elicit a powerful yet localized anti-tumor immune response.

Detalimogene voraplasmid has received Fast Track designation from the U.S. Food and Drug Administration (FDA) based on its potential to address a high unmet medical need for patients with BCG-unresponsive carcinoma in situ (CIS) NMIBC with or without resected papillary tumors who are unable to undergo cystectomy. Fast Track designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

Detalimogene was developed using the Company’s Dually Derivatized Oligochitosan (DDX) platform, a technology designed to transform how gene therapies are accessed by patients and utilized by clinicians. Medicines developed with the DDX platform can potentially overcome the limitations of viral-based gene therapies, simplify safe handling and cold storage complexities and streamline both manufacturing processes and administration paradigms.

About the Pivotal LEGEND Trial

Detalimogene voraplasmid is being evaluated in the ongoing, open-label, multi-cohort, Phase 2 LEGEND trial to establish its safety and efficacy in high-risk, non-muscle invasive bladder cancer (NMIBC). LEGEND’s pivotal cohort (Cohort 1) consists of approximately 100 patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC with carcinoma in situ (CIS) (with or without papillary disease) and is designed to serve as the basis of the Company’s Biologics License Application (BLA) filing. In addition to this pivotal cohort, three additional cohorts are actively enrolling patients, including NMIBC patients with CIS who are naïve to treatment with BCG (Cohort 2a); NMIBC patients with CIS who have been exposed to BCG, but have not received adequate BCG treatment (Cohort 2b); and BCG-unresponsive high-risk NMIBC patients with papillary-only disease (Cohort 3).

The LEGEND trial is actively enrolling patients with sites participating in the USA, Canada, Europe and the Asia-Pacific region. For more information, please visit TheLegendStudy.com.

On January 30, 2025 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, provides an update on its activities for the quarter ended 31 December 2024 (Q2 FY25) (Press release, Immutep, JAN 30, 2025, View Source [SID1234649968]).

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EFTI DEVELOPMENT PROGRAM FOR CANCER

TACTI-004 – Start of Phase III Trial in 1L NSCLC

In December 2024, Immutep initiated its pivotal TACTI-004 Phase III clinical trial of eftilagimod alfa ("efti") for the treatment of first-line metastatic non-small cell lung cancer (1L NSCLC). The receipt of regulatory approval from the Australian Therapeutic Goods Administration means that Immutep has transitioned into a Phase III company; a significant milestone for the Company.

Immutep has successfully completed regulatory submissions in the vast majority of the more than 25 countries that will be part of the global TACTI-004 trial. Additional approvals from multiple countries are expected in the weeks and months ahead. The Company expects to enrol the first patient in Q1 of CY2025.

TACTI-003 (KEYNOTE-C34) – Phase IIb Trial in 1L HNSCC

In December 2024, Immutep reported further positive results from Cohort B of the TACTI-003 (KEYNOTEC34) Phase IIb trial. Cohort B is evaluating efti in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC) with PD-L1 negative tumours (CPS <1) who typically do not respond well to anti-PD-1 therapy alone. The results were presented by Martin Forster, M.D., Ph.D., at the ESMO (Free ESMO Whitepaper) Immuno-Oncology (IO) Annual Congress 2024.

Adding to the high response rates and favourable safety data previously reported in July 2024, the new data showed that, encouragingly, median overall survival (OS) has not yet been reached and the 12- month OS rate is 67%. A promising progression-free survival (PFS) of 5.8 months, interim median duration of response (DOR) of 9.3 months, 35.5% objective response rate (ORR) and 58.1% disease control rate (DCR) were also reported. The complete response rate increased to 12.9% and 16.1%, according to RECIST 1.1 and iRECIST, respectively. This data compares favourably to historical results from anti-PD-1 therapy alone in 1L HNSCC patients with CPS <1. In addition, efti in combination with KEYTRUDA continues to be well-tolerated with no new safety signals. Immutep will continue to follow the maturing data from TACTI-003 and engage with regulatory authorities regarding potential paths forward.

AIPAC-003 – Phase II/III Trial in Metastatic Breast Cancer

In October 2024, Immutep completed patient enrolment in the Phase II portion of the AIPAC-003 trial. The randomised Phase II portion of the trial enrolled 65 metastatic hormone receptor positive (HR+), HER2-negative/low or triple-negative breast cancer patients who exhausted endocrine therapy including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Patients across 22 clinical sites in Europe and the United States have been randomised 1:1 to receive either 30mg or 90mg dosing of efti in combination with paclitaxel to determine the optimal biological dose consistent with the FDA’s Project Optimus initiative and prior regulatory interaction with FDA. Data cleaning and analysis is ongoing.

INSIGHT-003 – Phase I Trial in Non-Squamous 1L NSCLC

In November 2024, first overall survival results were reported from the investigator-initiated INSIGHT003 trial evaluating efti in combination with KEYTRUDA (pembrolizumab) and doublet chemotherapy as first-line treatment for patients with advanced or metastatic non-squamous non-small cell lung cancer (1L NSCLC).

Mature data from patients with a minimum follow-up of 22 months (N=21) demonstrated results significantly exceeding historical controls and expectations. Data included a median OS of 32.9 months, median PFS of 12.7 months, and a 24-month OS rate of 81.0%. Data from all evaluable patients to date (N=40) showed a marked improvement in ORR compared to historical controls. Safety remains favourable with no new safety signals reported.

Subsequent to quarter end, patient enrolment was completed for INSIGHT-003 in January 2025. The trial reached its enrolment target of approximately 50 evaluable patients across multiple clinical sites in Germany led by the Frankfurt Institute of Clinical Cancer Research IKF. Additional data updates are expected in 2025 and beyond.

EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma

Also in November, new data from the EFTISARC-NEO Phase II investigator-initiated trial of efti in combination with radiotherapy plus KEYTRUDA (pembrolizumab) for patients with soft tissue sarcoma (STS) were presented at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting.

Based on preliminary analysis, the triple combination therapy demonstrates significant efficacy in the neoadjuvant setting for resectable STS. The combination achieved a greater than three-fold increase in tumour hyalinization/fibrosis (median 50%) at the time of surgery as compared to a historical median of 15% from radiotherapy alone. In addition to being the primary endpoint of the EFTISARC-NEO study, the tumour hyalinization/fibrosis rate has also been identified as a predictor of overall survival for STS patients in the neoadjuvant setting.

The EFTISARC-NEO trial, with a data cut-off of 20 October 2024, also showed 71.4% of patients achieved a pathologic response defined as ≥35% of hyalinization/fibrosis and 9.5% of patients achieved a complete pathologic response. Additionally, the triple combination therapy is safe with no grade ≥3 toxicities related to efti and KEYTRUDA.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE

IMP761 is a first-in-class agonist LAG-3 antibody designed to restore balance to the immune system by enhancing the "brake" function of LAG-3 to silence dysregulated self-antigen-specific memory T cells that cause many autoimmune diseases.

In December 2024, Immutep reported favourable initial safety data from the placebo-controlled, double-blind first-in-human Phase I study evaluating IMP761. There have been no treatment related adverse events in the first three of five single ascending dose cohorts in healthy participants. Additional safety data and assessment of pharmacokinetic/pharmacodynamic (PK/PD) relationships to follow in the first half of CY2025.

PARTNER ACTIVITY

Collaboration with Monash University

In December 2024, new findings that resolve how human lymphocyte activation gene 3 (LAG-3) binds to its main ligand MHC Class II (MHC-II), also known as HLA Class II (HLA-II) in humans, were published in Science Immunology. The work by Monash University and Immutep, is also the first to show the crystal structure of a human LAG-3/MHC-II complex and provides a better foundation for development of blocking LAG-3 therapeutics, including Immutep’s anti-LAG-3 small molecule program.

INTELLECTUAL PROPERTY

During the quarter, Immutep was granted three new patents for efti and IMP761 in various territories. In particular, Immutep was granted a new patent for efti in combination with a PD-1 pathway inhibitor for the treatment of infection from the Brazilian Patent Office and a new patent for the same combination for the treatment of cancer or infection by the Japan Patent Office. In addition, a new patent was granted for IMP761 by the Malaysian Patent Office.

CORPORATE & FINANCIAL SUMMARY

Board & Senior Management Changes

Independent Non-Executive Director, Anne Anderson, tendered her resignation from the role, effective from 4 October 2024. The Board thanked her for her contribution to Immutep and wished her every success with her next endeavours.

As Immutep’s efti program has advanced into Phase III development, the Company has continued to grow and evolve its team. As part of this, Christian Mueller, who has been with Immutep for over eight years, most recently as SVP Regulatory and Strategy has been promoted to Chief Development Officer. In addition, Dr Florian Vogl, Immutep’s Chief Medical Officer will depart the Company in April 2025. The Company’s current Medical Affairs Advisor, who has been working in different roles closely with Immutep for over nine years, Dr Stephan Winckels, has been appointed acting CMO and taken over all related responsibilities.

Cash Flow Summary

During the quarter, Immutep continued to advance its clinical trial programs for efti and for IMP761. The Company is well funded with a strong cash, cash equivalent and term deposit balance as at 31 December 2024 of approximately A$159.26 million in total, which gives Immutep an expected cash reach to the end of CY2026. The A$159.26 million total balance consists of: 1) a cash and cash equivalent balance of $73.89 million and 2) bank term deposits totalling A$85.37 million, which have been recognised as short-term investments due to having maturities of more than 3 months and less than 12 months.

In Q2 FY25, cash receipts from customers were $8k. The net cash used in G&A activities in the quarter was $566k, compared to $961k in Q1 FY25. Payments to Related Parties (detailed in item 6.1 of the Appendix 4C) comprises Non-Executive Directors’ fees and Executive Directors’ remuneration of $344k.

The net cash used in R&D activities during the quarter was $16.2 million, compared to $9.5 million to Q1 FY25. The increase is mainly due to the increased level of clinical trial activities especially the commencement of the phase III TACTI-004 clinical trial. Payments for staff costs were $2.5 million in the quarter compared to $2.8 million in Q1 FY25.

Total net cash outflows used in operating activities in the quarter were $19.0 million compared to $8.6 million in Q1 FY25.

Total cash flow used in investing activities for the quarter was $30.4 million, mainly due to the net increase of $30.0 million in short-term investments. The short-term investments are comprised of term deposits with maturities of greater than 3 months and less than 12 months. During the quarter, the company invested $35.3 million in short-term investments and transferred back $5.3 million from shortterm investments that had matured to cash at bank, resulting in a net increase in short-term investments of $30.0 million.

On January 30, 2025 Novartis reported strong momentum of sales growth with margin expansion, reaches key innovation milestones in 2024 (Press release, Novartis, JAN 30, 2025, View Source [SID1234649967]).

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Full year

Net sales grew +12% (cc1, +11% USD) with core operating income1 up +22% (cc, +19% USD)
Sales growth driven by continued strong performance from Entresto (+31% cc), Cosentyx (+25% cc), Kesimpta (+49% cc), Kisqali (+49% cc), Pluvicto (+42% cc) and Leqvio (+114% cc)
Core operating income margin1 38.7%, +330 basis points (cc), mainly driven by higher net sales
Operating income grew +55% (cc, +49% USD); net income up +45% (cc, +39% USD)
Core EPS1 grew +24% (cc, +21% USD) to USD 7.81
Free cash flow1 of USD 16.3 billion (+24% USD) driven by higher net cash flows from operating activities
Fourth quarter

Net sales grew +16% (cc, +15% USD) with core operating income up +29% (cc, +27% USD)
Sales growth driven by continued strong performance from Entresto (+34% cc), Kesimpta (+49% cc), Kisqali (+52% cc), Cosentyx (+24% cc), and Leqvio (+83% cc)
Selected innovation milestones:
Scemblix FDA accelerated approval for 1L Ph+ CML-CP
Kisqali EC approval for HR+/HER2- stage II and III eBC
Fabhalta (iptacopan) FDA submission for C3G; priority review granted
OAV101 IT Phase III STEER study positive readout in SMA
Dividend, 2025 guidance

Dividend of CHF 3.50 per share, an increase of 6.1%, proposed for 2024
2025 guidance2 – Net sales expected to grow mid- to high-single digit and core operating income expected to grow high single to low double-digit
Basel, January 31, 2025 – commenting on Q4 2024 results, Vas Narasimhan, CEO of Novartis, said:
"In our first full year as a pure-play innovative medicines company, Novartis delivered one of the strongest financial performances in our history, growing sales 12% cc and core operating income 22% cc. We also achieved important innovation milestones, including new approvals and readouts for many of the assets that will fuel our growth over the mid- to long-term. With the momentum we are seeing in the business, we expect to continue our strong sales growth with margin expansion in 2025 and we remain on track to deliver on our mid-term guidance. Looking ahead, we are focused on executing against our pipeline, including 15 submission-enabling readouts over the coming years and more than 30 assets with the potential to drive differentiated growth over the long term. We remain balanced in our capital allocation approach and committed to creating sustainable value for shareholders."

Key figures Continuing operations3
Q4 2024 Q4 2023 % change FY 2024 FY 2023 % change
USD m USD m USD cc USD m USD m USD cc
Net sales 13 153 11 423 15 16 50 317 45 440 11 12
Operating income 3 530 2 582 37 39 14 544 9 769 49 55
Net income 2 820 2 638 7 6 11 939 8 572 39 45
EPS (USD) 1.42 1.29 10 10 5.92 4.13 43 49
Free cash flow 3 635 2 141 70 16 253 13 160 24
Core operating income 4 859 3 821 27 29 19 494 16 372 19 22
Core net income 3 933 3 126 26 29 15 755 13 446 17 21
Core EPS (USD) 1.98 1.53 29 33 7.81 6.47 21 24
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 47 of the Condensed 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 7.
3. As defined on page 35 of the Condensed Financial Report, Continuing operations include the retained business activities of Novartis, comprising the innovative medicines business and the continuing corporate activities, and Discontinued operations include operational results from the Sandoz business.

Strategy

Our focus

In 2023, Novartis completed its transformation into a "pure-play" innovative medicines business. 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.
Strengthening foundations: Unleashing the power of our people, scaling data science and technology and continuing to build trust with society.
Financials

Following the September 15, 2023, shareholder approval of the spin-off of Sandoz, Novartis reported its consolidated financial statements as "continuing operations" and "discontinued operations."

Continuing operations include the retained business activities of Novartis, comprising the innovative medicines business 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.

While the commentary below focuses on continuing operations, we also provide information on discontinued operations.

Continuing operations

Fourth quarter

Net sales were USD 13.2 billion (+15%, +16% cc), with volume contributing 15 percentage points to growth. Generic competition had a negative impact of 1 percentage point and pricing had a positive impact of 2 percentage points, benefiting from revenue deduction adjustments mainly in the US.

Operating income was USD 3.5 billion (+37%, +39% cc), mainly driven by higher net sales, partly offset by higher R&D investments.

Net income was USD 2.8 billion (+7%, +6% cc), mainly driven by higher operating income, partly offset by higher income taxes, mainly resulting from higher income before taxes in the current year and non-recurring tax benefits in the prior year. EPS was USD 1.42 (+10%, +10% cc), benefiting from the lower weighted average number of shares outstanding.

Core operating income was USD 4.9 billion (+27%, +29% cc), mainly driven by higher net sales, partly offset by higher R&D investments. Core operating income margin was 36.9% of net sales, increasing 3.4 percentage points (+3.7 percentage points cc).

Core net income was USD 3.9 billion (+26%, +29% cc), mainly due to higher core operating income. Core EPS was USD 1.98 (+29%, +33% cc), benefiting from the lower weighted average number of shares outstanding.

Free cash flow from continuing operations amounted to USD 3.6 billion (+70% USD), compared with USD 2.1 billion in the prior-year quarter, driven by higher net cash flows from operating activities from continuing operations.

Full year

Net sales were USD 50.3 billion (+11%, +12% cc), with volume contributing 14 percentage points to growth. Generic competition had a negative impact of 2 percentage points and pricing was flat.

Operating income was USD 14.5 billion (+49%, +55% cc), mainly driven by higher net sales, lower impairments, amortization and restructuring charges, partly offset by prior-year one-time income from legal matters and higher R&D investments.

Net income was USD 11.9 billion (+39%, +45% cc), mainly driven by higher operating income, partly offset by higher income taxes, mainly resulting from higher income before taxes in the current year and non-recurring tax benefits in the prior year. EPS was USD 5.92 (+43%, +49% cc), benefiting from the lower weighted average number of shares outstanding.

Core operating income was USD 19.5 billion (+19%, +22% cc), mainly driven by higher net sales, partly offset by higher R&D investments. Core operating income margin was 38.7% of net sales, increasing 2.7 percentage points (+3.3 percentage points cc).

Core net income was USD 15.8 billion (+17%, +21% cc), mainly due to higher core operating income. Core EPS was USD 7.81 (+21%, +24% cc), benefiting from the lower weighted average number of shares outstanding.

Free cash flow from continuing operations amounted to USD 16.3 billion (+24% USD), compared with USD 13.2 billion in 2023, driven by higher net cash flows from operating activities from continuing operations.

Discontinued operations

Discontinued operations include the Sandoz generic pharmaceuticals and biosimilars division, certain corporate activities attributable to Sandoz and certain other expenses related to the spin-off of the Sandoz business.

Fourth quarter

As the Sandoz spin-off was completed on October 3, 2023, there were no operating results in the fourth quarter of 2024 and 2023 related to discontinued operations. In the fourth quarter of 2023, net income from discontinued operations amounted to USD 5.8 billion, driven by the IFRS Accounting Standards non-cash, non-taxable, net gain on distribution of Sandoz Group AG to Novartis AG shareholders of USD 5.9 billion. For further details see Note 3 "Significant acquisitions of businesses and spin-off of Sandoz business" and Note 11 "Discontinued operations" to the condensed consolidated financial statements.

Full year

As the Sandoz spin-off was completed on October 3, 2023, there were no operating results in 2024 related to discontinued operations. In 2023, discontinued operations net sales were USD 7.4 billion, operating income amounted to USD 265 million and net income from discontinued operations was USD 6.3 billion driven by the IFRS Accounting Standards non-cash, non-taxable, net gain on distribution of Sandoz Group AG to Novartis AG shareholders, which amounted to USD 5.9 billion. For further details see Note 3 "Significant acquisitions of businesses and spin-off of Sandoz business" and Note 11 "Discontinued operations" to the condensed consolidated financial statements.

Total Company

Fourth quarter

Total Company net income was USD 2.8 billion in 2024, compared with USD 8.5 billion in 2023 and basic EPS was USD 1.42 compared to USD 4.14 in the prior year quarter as the prior year quarter included the IFRS Accounting Standards non-cash, non-taxable, net gain on distribution of Sandoz Group AG to Novartis AG shareholders, which amounted to USD 5.9 billion. Net cash flows from operating activities for total Company amounted to USD 4.2 billion and free cash flow amounted to USD 3.6 billion.

Full year

Total Company net income was USD 11.9 billion in 2024, compared with USD 14.9 billion in 2023 and basic EPS was USD 5.92 compared to USD 7.15 in the prior year as the prior year included the IFRS Accounting Standards non-cash, non-taxable, net gain on distribution of Sandoz Group AG to Novartis AG shareholders, which amounted to USD 5.9 billion. Net cash flows from operating activities for total Company amounted to USD 17.6 billion and free cash flow amounted to USD 16.3 billion.

Q4 key growth drivers

Underpinning our financial results in the quarter is a continued focus on key growth drivers (ranked in order of contribution to Q4 growth) including:

Entresto (USD 2 180 million, +34% cc) sustained robust, demand-led growth, with increased penetration in the US and Europe following guideline-directed medical therapy in heart failure, and in China and Japan with increased penetration in hypertension
Kesimpta (USD 950 million, +49% cc) sales grew across all regions reflecting increased demand for a high efficacy product with convenient self-administered dosing
Kisqali (USD 902 million, +52% cc) sales grew strongly across all regions, including +66% (cc) growth in the US with strong momentum from the recently launched early breast cancer (eBC) indication. Kisqali growth is underpinned by increasing recognition of its overall survival benefit in HR+/HER2- metastatic breast cancer (mBC) as well as Category 1 NCCN Guidelines recommendation in both mBC and eBC
Cosentyx (USD 1 596 million, +24% cc) sales grew mainly in the US, Europe and emerging growth markets driven by recent launches (including the HS indication and the IV formulation in the US) and volume growth in core indications
Leqvio (USD 223 million, +83% cc) continued to show steady growth, with a focus on increasing account and patient adoption, and continuing medical education
Scemblix (USD 207 million, +66% cc) sales grew across all regions demonstrating the continued high unmet need in CML
Pluvicto (USD 351 million, +28% cc) sales grew in Europe and in the US. With supply now unconstrained, the focus is on increasing share in established RLT sites while opening new sites and referral pathways and initiating new patients
Fabhalta (USD 57 million) launch continues with a modest ramp in PNH globally and in IgA nephropathy in the US
Jakavi (USD 487 million, +13% cc) sales grew across all regions driven by strong demand across indications
Tafinlar + Mekinist (USD 527 million, +10% cc) sales grew mainly in the US, Japan and emerging growth markets driven by increased demand
Lutathera (USD 190 million, +30% cc) sales grew across all regions due to increased demand and earlier line adoption (within indication) in the US and Japan
Ilaris (USD 413 million, +11% cc) sales grew across all regions, led by the US
Xolair (USD 399 million, +9% cc) grew mainly in emerging growth markets
Emerging growth markets* Grew +9% (cc) overall. China grew +7% (cc) to USD 0.8 billion, mainly driven by Entresto, Xolair and Kisqali
*All markets except the US, Canada, Western Europe, Japan, Australia, and New Zealand

Net sales of the top 20 brands in the fourth quarter and full year

Q4 2024 % change FY 2024 % change
USD m USD cc USD m USD cc
Entresto 2 180 33 34 7 822 30 31
Cosentyx 1 596 22 24 6 141 23 25
Kesimpta 950 48 49 3 224 49 49
Kisqali 902 48 52 3 033 46 49
Promacta/Revolade 583 4 5 2 216 -2 -1
Tafinlar + Mekinist 527 8 10 2 058 7 9
Jakavi 487 10 13 1 936 13 15
Tasigna 411 -8 -6 1 671 -10 -8
Xolair 399 6 9 1 643 12 15
Ilaris 413 10 11 1 509 11 14
Pluvicto 351 29 28 1 392 42 42
Sandostatin Group 306 -3 -1 1 279 -3 -1
Zolgensma 262 -8 -6 1 214 0 2
Lucentis 210 -30 -29 1 044 -29 -28
Leqvio 223 81 83 754 112 114
Lutathera 190 29 30 724 20 20
Exforge Group 159 2 8 703 -1 2
Scemblix 207 66 66 689 67 68
Galvus Group 144 -6 2 602 -13 -6
Diovan Group 140 -5 -2 590 -4 0
Top 20 brands total 10 640 19 21 40 244 18 19
R&D update – key developments from the fourth quarter

New approvals

Scemblix
(asciminib) FDA granted accelerated approval to Scemblix for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). The FDA also broadened the indication for Scemblix to include adult patients with previously treated Ph+ CML-CP.
Kisqali
(ribociclib) EC approved Kisqali as an adjuvant treatment in combination with an aromatase inhibitor for patients with HR+/HER2- early breast cancer (eBC) at high risk of recurrence regardless of nodal status, nearly doubling the eligible population.
Regulatory updates

Fabhalta
(iptacopan) Submission for the treatment of C3 glomerulopathy (C3G) was completed in the US, and the FDA granted Priority Review status to Fabhalta in this indication. The FDA also confirmed no need for an Advisory Committee meeting.
Results from ongoing trials and other highlights

OAV101 IT
(onasemnogene abeparvovec) Novartis announced positive topline results from the Phase III STEER study. This pivotal trial assessed the efficacy and safety of investigational intrathecal OAV101 in treatment-naïve patients with spinal muscular atrophy (SMA) Type 2, aged two to less than 18 years who are able to sit but have never walked independently. The study met its primary endpoint showing an increase from baseline across the study population in total Hammersmith Functional Motor Scale – Expanded (HFMSE) scores. HFMSE is a gold standard for SMA-specific assessment of motor ability and disease progression.
Pluvicto
(lutetium Lu177 vipivotide tetraxetan) Final overall survival (OS) analysis in the Phase III PSMAfore study in pre-taxane mCRPC demonstrated an OS hazard ratio less than 1.0 (HR<1.0) in the intent-to-treat (ITT) population unadjusted for cross-over. These results have been shared with the FDA as part of their ongoing review of Pluvicto in this indication.
Kisqali
(ribociclib) Results from an updated analysis of the pivotal Phase III NATALEE trial of Kisqali plus endocrine therapy (ET) in patients with HR+/HER2- stage II and III eBC showed a sustained reduction in distant recurrence of 28.5% compared to ET alone, underscoring Kisqali’s extended efficacy beyond its 3-year treatment duration. No new safety signals were identified. Data presented at SABCS.

In addition, Kisqali was recognized by NCCN Guidelines as a Category 1 preferred therapy in combination with an aromatase inhibitor for patients with HR+/HER2- eBC. Kisqali is the only Category 1 preferred CDK4/6 inhibitor recommended for both all node-positive disease as well as node-negative disease with high-risk disease characteristics. Kisqali also achieved the highest score (A) on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) for eBC, while maintaining a rating of 5 and 4 in the mBC setting.

In January 2025, Novartis settled compound patent litigation with a generic manufacturer, supporting Kisqali US patent protection until at least Q1 2031.
Scemblix
(asciminib) 96-week results from the Phase III ASC4FIRST trial with Scemblix showed sustained superior major molecular response vs. all investigator-selected standard-of-care TKIs (imatinib, nilotinib, dasatinib and bosutinib) and vs. imatinib alone in adult patients with newly diagnosed Ph+ CML-CP. Fewer treatment-related grade ≥3 AEs and half the rate of AEs leading to treatment discontinuation were reported for Scemblix vs. both imatinib and second-generation TKIs. Data presented at ASH (Free ASH Whitepaper).
Fabhalta
(iptacopan) In the Phase III APPEAR-C3G study, patients with C3G treated with oral Fabhalta in addition to supportive care experienced clinically meaningful proteinuria reduction sustained at 12 months. In addition, in the open-label period of the study, proteinuria reduction was seen in participants switched to Fabhalta, and improvement in estimated glomerular filtration rate (eGFR) slope was observed upon Fabhalta initiation compared to patients’ historic rapid decline. Fabhalta continued to show a favorable safety profile. Data presented at ASN.
Selected transactions Novartis entered into a global license and collaboration agreement with PTC Therapeutics for PTC518, a HTT mRNA splice modulator with the potential to become the first oral disease-modifying therapy for Huntington’s disease. Under the agreement, Novartis will assume responsibility for PTC518’s development, manufacturing and commercialization following the completion of the placebo-controlled portion of the ongoing Phase II PIVOT-HD study, expected in H1 2025.

Novartis acquired Kate Therapeutics, a preclinical-stage biotechnology company focused on developing adeno-associated virus (AAV)-based gene therapies to treat genetically defined neuromuscular diseases. The acquisition will strengthen Novartis’ efforts to advance gene therapies and neuroscience innovation and includes enabling technology platforms and several preclinical therapeutic candidates.

Novartis entered into a worldwide licensing and collaboration agreement with Ratio Therapeutics for a next-generation SSTR2-targeting radiotherapeutic candidate. The collaboration focuses on preclinical research and selection of an SSTR2-targeting development candidate, after which Novartis will lead development, manufacturing and commercialization.
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 2024, Novartis repurchased a total of 77.5 million shares for USD 8.3 billion on the SIX Swiss Exchange second trading line. These purchases included 68.8 million shares (USD 7.3 billion) under the up-to USD 15 billion share buyback announced in July 2023 (with up to USD 5.4 billion still to be executed). In addition, 8.7 million shares (USD 1.0 billion) were repurchased to mitigate the impact of share deliveries under the equity-based compensation plans for employees. Furthermore, 1.2 million shares (equity value of USD 0.1 billion) were repurchased from employees. In the same period, 9.8 million shares (equity value of USD 1.1 billion) were delivered to employees related to equity-based compensation plans. Consequently, the total number of shares outstanding decreased by 68.9 million versus December 31, 2023. These treasury share transactions resulted in an equity decrease of USD 7.4 billion and a net cash outflow of USD 8.3 billion.

Net debt increased to USD 16.1 billion at December 31, 2024, compared to USD 10.2 billion net debt at December 31, 2023. The increase was mainly due to the free cash flow of USD 16.3 billion being more than offset by the cash outflows for treasury share transactions of USD 8.3 billion, the annual dividend payment of USD 7.6 billion, and net cash outflow for M&A / intangible assets transactions of USD 6.3 billion.

As of Q4 2024, the long-term credit rating for the company is Aa3 with Moody’s Ratings and AA- with S&P Global Ratings.

2025 outlook

Barring unforeseen events; growth vs prior year in cc
Net sales Expected to grow mid- to high-single digit
Core operating income Expected to grow high single to low double-digit
Key assumptions:

We assume Tasigna, Promacta and Entresto US generic entry mid-2025 for forecasting purposes
Foreign exchange impact

If late-January exchange rates prevail for the remainder of 2025, the foreign exchange impact for the year would be negative 2 percentage points on net sales and negative 3 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website.

Annual General Meeting

Dividend Proposal

The Novartis Board of Directors proposes a dividend payment of CHF 3.50 per share for 2024, up 6.1% from CHF 3.30 per share in the prior year, representing the 28th consecutive dividend increase since the creation of Novartis in December 1996. Shareholders will vote on this proposal at the AGM on March 7, 2025.

Reduction in Share Capital

The Novartis Board of Directors proposes to cancel 77 508 630 shares (8 548 613 shares repurchased under the authorization of March 4, 2022, and 68 960 017 shares repurchased under the authorization of March 7, 2023) and to reduce the share capital accordingly by CHF 38.0 million, from CHF 1 073 065 943.53 to CHF
1 035 086 714.83.

Potential Further Share Repurchases

As of December 31, 2024, the remaining available amount under the existing shareholder authority granted at the 2023 AGM is CHF 3.5 billion. To allow for the full execution of the already announced share buyback of up to USD 15 billion and potential additional share buybacks, the Board of Directors proposes that shareholders, in addition to the remaining authorization of CHF 3.5 billion, authorize the Board of Directors to repurchase shares as deemed appropriate from time to time up to CHF 10 billion between the 2025 AGM and 2028 AGM.

Elections of the Board Chair and the Members of the Board of Directors

Dr. Joerg Reinhardt, Dr. Charles Sawyers and Mr. William Winters are not standing for re-election. The Board of Directors and the Executive Committee of Novartis thank them for their many years of valuable service as Chair and members of the Board of Directors.

The Board of Directors proposes the election of Dr. Giovanni Caforio as member of the Board of Directors and Board Chair. Dr. Caforio has had an international career in the healthcare industry spanning more than 35 years, most recently as the Chairman and CEO of Bristol Myers Squibb (BMS).

In addition, the Board of Directors proposes the re-election of the current members of the Board of Directors with the exception of Dr. Reinhardt, Dr. Sawyers and Mr. Winters, and the election of Dr. Elizabeth McNally as a new member of the Board of Directors, each until the end of the next Annual General Meeting.

Key figures1

Continuing operations2 Q4 2024 Q4 2023 % change FY 2024 FY 2023 % change
USD m USD m USD cc USD m USD m USD cc
Net sales 13 153 11 423 15 16 50 317 45 440 11 12
Operating income 3 530 2 582 37 39 14 544 9 769 49 55
As a % of sales 26.8 22.6 28.9 21.5
Net income 2 820 2 638 7 6 11 939 8 572 39 45
EPS (USD) 1.42 1.29 10 10 5.92 4.13 43 49
Cash flows from
operating activities 4 193 2 547 65 17 619 14 220 24
Non-IFRS measures
Free cash flow 3 635 2 141 70 16 253 13 160 24
Core operating income 4 859 3 821 27 29 19 494 16 372 19 22
As a % of sales 36.9 33.5 38.7 36.0
Core net income 3 933 3 126 26 29 15 755 13 446 17 21
Core EPS (USD) 1.98 1.53 29 33 7.81 6.47 21 24



Discontinued operations2 Q4 2024 Q4 2023 % change FY 2024 FY 2023 % change
USD m USD m USD cc USD m USD m USD cc
Net sales nm nm 7 428 nm nm
Operating income nm nm 265 nm nm
As a % of sales 3.6
Net income 5 842 nm nm 6 282 nm nm
Non-IFRS measures
Core operating income nm nm 1 185 nm nm
As a % of sales 16.0
Core net income nm nm 889 nm nm



Total Company Q4 2024 Q4 2023 % change FY 2024 FY 2023 % change
USD m USD m USD cc USD m USD m USD cc
Net income 2 820 8 480 nm nm 11 939 14 854 nm nm
EPS (USD) 1.42 4.14 nm nm 5.92 7.15 nm nm
Cash flows from
operating activities 4 193 2 547 nm nm 17 619 14 458 nm nm
Non-IFRS measures
Free cash flow 3 635 2 141 nm nm 16 253 13 179 nm nm
Core net income 3 933 3 126 nm nm 15 755 14 335 nm nm
Core EPS (USD) 1.98 1.53 nm nm 7.81 6.90 nm nm

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 47 of the Condensed Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.
2. As defined on page 35 of the Condensed Financial Report, Continuing operations include the retained business activities of Novartis, comprising the innovative medicines business 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 Financial Report at the link below:
View Source

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Date / Time:

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