University of Insubria

Exploratory analysis from Cohort 3 of the Phase 2 REFINE study presented in an oral session at ASH NORTH CHICAGO, Ill., Dec. 10, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new data from Cohort 3 of its Phase 2 REFINE study of investigational navitoclax in combination with ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (MF). The exploratory analysis suggests the combination of navitoclax and ruxolitinib led to reductions in bone marrow fibrosis (BMF) and variant allele frequency (VAF) for common genetic mutations found in individuals with myelofibrosis that may indicate potential disease modification.1 The findings were shared in an oral presentation (abstract #237) at the 64th American Society of Hematology Annual Meeting & Exposition (ASH). "While the current standard of care for patients with myelofibrosis can improve disease symptoms, impact on underlying disease biology is limited. It is our hope that patients have an option that goes beyond symptom control," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology clinical development, AbbVie. "Consistent with previous evidence, these results suggest navitoclax combination may have disease modifying potential, both as an anti-fibrosis agent and by reducing variant allele frequency of driver mutations." REFINE (NCT03222609) is a Phase 2 non-randomized open-label multi-cohort study evaluating the safety and efficacy of navitoclax alone or in combination with ruxolitinib in MF.2 These data build on AbbVie's history of transforming standards of care in blood cancers, including recent presentations of investigational navitoclax data from the REFINE study earlier this year at the American Association for Cancer Research (AACR) Annual Meeting and the European Hematology Association (EHA) Annual Congress. The findings presented at ASH were based on an exploratory analysis of 32 JAK inhibitor-naïve patients with MF from Cohort 3 of the Phase 2 REFINE study. The primary endpoint was spleen volume reduction of ≥35 percent (SVR35) from baseline at week 24.1 Key secondary and exploratory endpoints evaluated in this analysis were a reduction in BMF and a reduction in VAF for the driver gene mutations (JAK2V617, CALR, MPL or Triple-negative), respectively.1 In this exploratory analysis, SVR35 at week 24 was observed in higher-risk groups, improving over time. The four poor prognosis subgroups were: Type (primary or secondary) of MF (primary MF, 59 percent [n = 10/17]; age (≥75 years, 50 percent [n = 4/8]); prognostic risk score, as measured by Dynamic International Prognostic Scoring System or DIPSS (intermediate-2, 63 percent [n = 12/19]; high, 33 percent [n = 1/3]); and presence of high molecular risk (HMR) mutations (47 percent [n = 9/19].1 In Cohort 3, BMF grade improvement was evaluable in 81 percent (26/32) of patients.1 Of these study participants, 35 percent (9/26) achieved ≥ 1 grade improvement at any time during treatment with a median time-to-improvement of 12.3 weeks.1 Complete resolution of BMF was observed in 22 percent (2/9) of patients.1 Reduction in driver gene mutation VAF > 20% from baseline at week 12 or 24 was observed in 50 percent (14/28) of patients, while 18 percent (5/28) of patients achieved > 50% VAF reduction from baseline. There were no differences in > 20% VAF reductions from baseline to week 12 or 24 between those with or without HMR mutations (47 percent [7/15] versus 54 percent [7/13], respectively). Preliminary safety analysis identified no new safety signals. Twenty-five (78 percent) patients reported one or more adverse events (AE). The most common grade ≥3 AEs were thrombocytopenia (47 percent), anemia (34 percent), and neutropenia (25 percent). 9.4 percent of patients discontinued therapy due to an AE.3 "These results are promising for patients who need a treatment option that goes beyond just symptom control," said Francesco Passamonti, full professor of hematology, University of Insubria and chief, hematology, Varese Hospital, Italy. "The suggestion of disease modification in this analysis from combination therapy with navitoclax is encouraging, particularly when combined with clinical efficacy in terms of SVR35 rates in the higher risk groups that improved over time." About Navitoclax Navitoclax is an investigational, oral BCL-XL/BCL-2 inhibitor. Navitoclax is not approved by any health authority worldwide at this time. Its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies. AbbVie has an extensive late-stage clinical trial program for investigational navitoclax that is currently enrolling. Please visit us here for more information about enrolling in a clinical trial. About the REFINE Study REFINE is a multi-cohort, Phase 2, randomized, open-label, multicenter study evaluating the tolerability and efficacy of navitoclax alone or when added to ruxolitinib in patients with myelofibrosis (MF).2 The primary outcome measure is the percentage of patients who achieve spleen volume reduction of greater than or equal to 35 percent (SVR35) from baseline to week 24.2 Secondary outcomes measures include percentage of participants achieving 50 percent reduction in total symptom score from baseline to week 24; anemia response every 12 weeks up to approximately 96 weeks, measured according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria; and change in grade of bone marrow fibrosis assessed according to the European Consensus Grading System.2 Data presented at ASH 2022 include safety and efficacy results from Cohort 3 of REFINE (n=32). Patients in Cohort 3 had primary or secondary MF with splenomegaly (DIPSS ≥ intermediate-1) and had not received JAK-2 therapy or bromodomain and extra terminal motif (BET) inhibitors prior to enrollment. The primary endpoint of SVR35 was assessed by MRI conducted by central review. Key secondary and exploratory endpoints evaluated in this analysis were a reduction in BMF obtained from BM biopsies by local evaluation and a reduction in VAF for the driver gene mutations (JAK2V617, CALR, or MPL), respectively. Studied HMR mutations included ASXL1, EZH2, SRSF2, IDH1/2, and U2AF1 p.Q157. Driver gene VAF and HMR mutations were determined in whole blood with a 50-gene focus myeloid next-generation sequencing panel. The findings presented at ASH 2022 are representative of data from Cohort 3 of the REFINE study as of February 7, 2022. More information about the REFINE study can be found at (NCT03222609). About Myelofibrosis Myelofibrosis (MF) is a rare, difficult-to-treat blood cancer that results in excessive scar tissue formation (fibrosis) in the bone marrow. Patients living with MF experience symptoms such as an enlarged spleen, fatigue, weakness, and severe anemia which are often debilitating and greatly impact quality of life. MF also carries a risk of transformation to more aggressive disease such as acute myeloid leukemia.4 About AbbVie in Oncology At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit and our Blood Cancer Press Kit page. About AbbVie AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2021 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. References: Passamonti F, Foran J, Tandra A, et al. The Combination of Navitoclax and Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Mediates Responses Suggestive of Disease Modification. [Oral Presentation #237]. Presented at 2022 American Society of Hematology (ASH) Annual Meeting and Exhibition, December 10-13, 2022. ClinicalTrials.gov. A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis (REFINE). NCT03222609. Available at . Last accessed October 2022. Navitoclax plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: Preliminary safety and efficacy in a multicenter, open-label Phase 2 study. [Oral Presentation S197]. Presented at European Hematology Association 2022 Congress (EHA 2022), June 9-12, 2022. Tsujimoto Y. (1998). Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria?. Genes to cells: devoted to molecular & cellular mechanisms, 3(11), 697–707. SOURCE AbbVie

Leiden University Medical Center joins global network of partners in the development of Philips Spectral Angio CT suite and its use in clinical research, bringing spectral CT imaging technology into an integrated hybrid angio CT suite with the aim of innovating a range of treatment procedures CIRSE 2022 presentation by University of Insubria (Varese, Italy) details positive results of study that uses spectral CT to better guide lung tumor biopsies Philips and University of Pennsylvania announce collaboration to investigate spectral CT guidance during interventional oncology procedures and its potential to confirm treatment effectiveness in real time Amsterdam, the Netherlands – Royal Philips (NYSE: PHG, AEX: PHIA), a global leader in health technology, today announced new milestones in the development of the world’s first spectral detector angio CT solution - Philips Spectral Angio CT suite - bringing the company’s breakthrough spectral CT imaging technology into an integrated hybrid angio CT suite. By combining its award-winning [1] Spectral CT 7500 system and its Image Guided Therapy System – Azurion with FlexArm – in a fully integrated interventional suite solution, Philips aims to give physicians immediate access to these two key imaging modalities in a single room, enabling innovation in minimally-invasive procedures in areas such as oncology, stroke, and trauma care. Philips today announced a new clinical partner and highlighted clinical studies that focus on the added value of using spectral CT imaging technology during interventional procedures. Expanding Philips’ clinical network Leiden University Medical Center (Leiden, the Netherlands) has joined Philips’ global network of clinical partners to investigate how its spectral detector angio CT solution could potentially offer new treatment opportunities and improve patient care. “We are excited to co-create an innovation that could play a defining role in improving patient care in the space of interventional oncology,” said Mark Burgmans, MD, Head of Interventional Radiology at Leiden University Medical Center. “Adding spectral CT imaging to the interventional suite will enable us to offer new treatment opportunities, avoid moving patients from one imaging suite to another, and offer the unique benefits of spectral CT information when you need it.” Other leading clinical institutes that Philips is working with on this innovation are Mayo Clinic (Rochester, MN, U.S.) and Baptist Health’s Miami Cardiac & Vascular Institute (Miami, FL, U.S.). Philips Spectral Angio CT suite combines the company’s latest diagnosis and treatment technologies. Philips Image Guided Therapy System – Azurion with FlexArm – is the company’s next-generation image-guided therapy platform, integrating best in class imaging systems, software, and specialized diagnostic and therapeutic devices to support exceptional treatment for the most complex procedures. The addition of Philips’ award-winning Spectral CT 7500 system means physicians only need one scan to capture all the spectral information required to differentiate and quantify different tissues. Spectral CT enables improved detection, delineation, and quantification of lesions, leading to better-informed planning for minimally-invasive procedures and more precise interventions. It has already proved its worth in other areas of oncology - for example, it has demonstrated higher sensitivity in detecting malignant findings and improved readings of incidental findings [2][3]. With its ability to improve tissue characterization, the Spectral CT 7500 offers significant benefits over conventional CT. Through continuous research, Philips is building clinical evidence that supports the added value of spectral CT imaging for diagnosis and treatment guidance. Research results show better targeted biopsies using spectral CT guidance At this year’s Cardiovascular and Interventional Radiological Society of Europe Annual Meeting (CIRSE 2022, September 10-14, Barcelona, Spain) a presentation is being given by Filippo Piacentino, interventional radiologist at the University of Insubria (Varese, Italy), on the value of spectral CT imaging guidance for performing high-confidence tumor biopsies [4]. The results being presented illustrate the potential for Philips’ spectral CT technology to better guide biopsies by distinguishing between active and non-active regions in a tumor. Ensuring that a biopsy contains a high number of actively dividing cancer cells is important for high-confidence diagnosis. “With conventional CT, large masses may appear as a largely uniform mass, making highly targeted biopsy difficult,” said Filippo Piacentino. “By fusing images from Philips’ XperGuide live needle guidance with images from spectral CT, that are color-coded based on the effective atomic number of tissues and provide a large amount of additional information, we can now investigate the possibility of obtaining better defined biopsy targets with a fewer number of inconclusive biopsies.” New clinical collaboration on reduction of the risk of tumor recurrence Philips also today announced a research collaboration with the University of Pennsylvania (Pennsylvania, PA, U.S.) to study the practicality of using spectral CT-based tissue temperature mapping to provide real-time feedback during tumor thermal ablation procedures to confirm its effectiveness before the patient leaves the room. This will potentially reduce the risk of localized tumor recurrence. “Announcing these important milestones in the development of our unique Philips Spectral Angio CT suite shows our strong commitment and progress in co-creating the future of image-guided therapy,” said Karim Boussebaa, General Manager of Image Guided Therapy Systems at Philips. “By combining the best of our award-winning modalities into a single suite we aim to unlock new treatment approaches that could benefit both patients and their physicians.” Visit Philips at CIRSE 2022 To learn more about Philips Spectral Angio CT suite, visit Philips at CIRSE 2022 and join the Philips symposia in which leading physicians will share their latest clinical insights on using this new imaging approach in interventional oncology. You can register via our dedicated CIRSE 2022 webpage. [1] Minnie Award for Best New Radiology Device [2] Analysis by Aarhus University Hospital Aarhus, Denmark. Results from case studies are not predictive of results in other cases. Results in other cases may vary. [3] Analysis by University Hospital Cleveland, USA. Results from case studies are not predictive of results in other cases. Results in other cases may vary. [4] Filippo Piacentino, ‘Spectral CT as innovative imaging guidance in large lesions lung biopsies. XperGuide and Z-effective fusion for more defined targets, more diagnostic samplings and more biomarkers information’. CIRSE 2022 Joost Maltha Philips Global Press Office Tel: +31 6 10 55 8116 Email: joost.maltha@philips.com Fabienne van der Feer Philips Image Guided Therapy Tel.: +31 622 698 001 E-mail: fabienne.van.der.feer@philips.com About Royal Philips Royal Philips (NYSE: PHG, AEX: PHIA) is a leading health technology company focused on improving people's health and well-being, and enabling better outcomes across the health continuum – from healthy living and prevention, to diagnosis, treatment and home care. Philips leverages advanced technology and deep clinical and consumer insights to deliver integrated solutions. Headquartered in the Netherlands, the company is a leader in diagnostic imaging, image-guided therapy, patient monitoring and health informatics, as well as in consumer health and home care. Philips generated 2021 sales of EUR 17.2 billion and employs approximately 79,000 employees with sales and services in more than 100 countries. News about Philips can be found at . Attachment Philips Spectral Angio CT suite

Researchers have proposed that the micromasers can serve as excellent model for future quantum batteries. Quantum technologies, i.e. technological devices obtained by building and manipulating quantum mechanical systems, are becoming a reality in recent days. The most prominent example is certainly given by quantum computers, where the unit of information, the bit, is replaced by its quantum mechanical counterpart, informally called the qubit. Contrary to classical computers, quantum computers promise to use the full quantum mechanical features of qubits, in order to address and solve computational problems which would be out of reach by using classical computers. As an example, the Canadian company Xanadu recently claimed that its quantum computer has been able to solve, in just 36 microseconds, a computational task that would have required 9000 years using state-of-the-art supercomputers. Quantum technologies need energy to operate. This simple consideration has led researchers, in the last ten years, to develop the idea of quantum batteries, which are quantum mechanical systems used as energy storage devices. In the very recent past, researchers at the Center for Theoretical Physics of Complex Systems (PCS) within the Institute for Basic Science (IBS), South Korea have been able to put tight constraints on the possible charging performance of a quantum battery. Specifically, they showed that a collection of quantum batteries can lead to an enormous improvement in charging speed compared to a classical charging protocol. This is thanks to quantum effects, which allow the cells in quantum batteries to be charged simultaneously. Despite these theoretical achievements, the experimental realizations of quantum batteries are still scarce. The only recent notable counter-example used a collection of two-level systems (very similar to the qubits just introduced) for energy storage purposes, with the energy being provided by an electromagnetic field (a laser). Given the current situation, it is clearly of uttermost importance to find new and more accessible quantum platforms which can be used as quantum batteries. With this motivation in mind, researchers from the same IBS PCS team, working in collaboration with Giuliano Benenti (University of Insubria, Italy), recently decided to revisit a quantum mechanical system that has been studied heavily in the past: the micromaser. Micromaser is a system where a beam of atoms is used to pump photons into a cavity. Put in simple terms, a micromaser can be thought of as a configuration specular to the experimental model of quantum battery mentioned above: the energy is stored into the electromagnetic field, which is charged by a stream of qubits sequentially interacting with it. The IBS PCS researchers and their collaborator showed that micromasers have features that allow them to serve as excellent models of quantum batteries. One of the main concerns when trying to use an electromagnetic field to store energy is that in principle, the electromagnetic field could absorb an enormous amount of energy, potentially much more than what is necessary. Making an analogy with a simple case, this would correspond to a phone battery that, when plugged, continues to increase its charge indefinitely. In such a scenario, forgetting that the phone is plugged in could be extremely risky, since there would be no mechanism to stop the charging. Luckily, the team's numerical results show that this cannot happen in micromasers. The electromagnetic field reaches quickly a final configuration (technically called a steady state), whose energy can be determined and decided a priori when building the micromaser. This property ensures protection from the risks of overcharging. In addition, the researchers showed that the final configuration of the electromagnetic field is in a pure state, which means that it brings no memory of the qubits that have been used during the charging. This latter property is particularly crucial when dealing with a quantum battery. It ensures that all the energy stored in the battery can be extracted and used whenever necessary, without the need of keeping track of the qubits used during the charging process. Finally, it was shown that these appealing features are robust and are not destroyed by changing the specific parameters defined in this study. This property is of clear importance when trying to build an actual quantum battery since imperfections in the building process are simply unavoidable. Interestingly, in a parallel series of papers, Stefan Nimmrichter and his collaborators have shown that quantum effects can make the charging process of the micromaser faster than classical charging. In other words, they have been able to show the presence of the previously mentioned quantum advantage during the charging of a micromaser battery. All these results suggest that micromaser could be considered as a promising new platform that can be used to build quantum batteries. The fact that these systems have been already implemented in experimental realizations for many years could give a serious boost in building new accessible prototypes of quantum batteries. To this end, the IBS PCS researchers and Giuliano Benenti are currently starting a joint collaboration with Stefan Nimmrichter and his collaborators, to further explore these promising models. The hope is that this new research collaboration will finally be able to benchmark and experimentally test the performances of micromaser-based quantum battery devices.