The purpose of this study is:
1. To provide continued pelabresib treatment to patients who have previously received pelabresib in a parent study and continue collecting safety and efficacy information
2. To evaluate the overall survival and leukemia-free survival of patients who discontinued placebo or pelabresib treatment in pelabresib parent studies

Start Date13 Aug 2024

Sponsor / Collaborator

Constellation Pharmaceuticals, Inc.

NCT05391022

/ CompletedPhase 1

A Phase 1, 2-Part Study to Evaluate the Effect of Food on Pharmacokinetics of Pelabresib (CPI-0610) and the Effect of Pelabresib on QTc in Patients With Advanced Malignancies

Phase 1 2-part study to evaluate the effect of food on pharmacokinetics of pelabresib (CPI-0610) and the effect of pelabresib on QTc in patients with advanced malignancies

Start Date20 Jul 2021

Sponsor / Collaborator

Constellation Pharmaceuticals, Inc.

NCT04603495

/ Active, not recruitingPhase 3

A Phase 3, Randomized, Double-blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients

A Phase 3, randomized, blinded study comparing pelabresib (CPI-0610) and ruxolitinib with placebo and ruxolitinib in myelofibrosis (MF) patients that have not been previously treated with Janus kinase inhibitors (JAKi). Pelabresib is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

Start Date09 Apr 2021

Sponsor / Collaborator

Constellation Pharmaceuticals, Inc.

100 Clinical Results associated with Pelabresib

100 Translational Medicine associated with Pelabresib

100 Patents (Medical) associated with Pelabresib

Literatures (Medical) associated with Pelabresib

01 Mar 2025·Current medicinal chemistry

A Combination of CPI-0610 and SAHA Induces Apoptosis through STAT3 and p38 Signalling Pathways in Diffuse Large B-cell Lymphoma Cells

Article

Author: Xu, Kailin ; Yan, Dongmei ; Xu, Linyan ; Qin, Yuanyuan ; Liu, Mengdi ; Sang, Wei ; Jiao, Jun ; Zhang, Meng

Background:::

Although immunotherapies have greatly improved diffuse large B-cell lymphoma (DLBCL) prognosis, a proportion of patients remain to be relapsed or refractory. Therefore, the identification of novel therapeutic targets and drugs is urgently required. Inhibition of the bromodomain and extra-terminal (BET) proteins has been a promising therapeutic strategy for various haematologic cancers. CPI-0610 is a potent and selective BET inhibitor. The effects of CPI-0610 in DLBCL cells have not been reported yet.

Aims::

The aim of this study was to assess the effects of CPI-0610 in DLBCL and its underlying mechanisms.

Methods::

DLBCL cells were treated with CPI-0610, followed by measuring cell viability, cell cycle, apoptosis, autophagy, and specific cell signaling pathways. Moreover, immunodeficient mice were engrafted with SUDHL2 cells and then treated with CPI-0610 for analysis of tumor burden. We also analyzed the synergistic effect of CPI-0610 with histone deacetylase inhibitor suberoylanilide hydroxamic acid.

Results::

The present study demonstrated that CPI-0610 displayed cell cytotoxicity by arresting the G1 cell cycle and inducing endogenous and exogenous apoptotic pathways. Additionally, CPI-0610 decreased BRD4 and c-Myc expressions and affected MAPK, JAK/STAT, and AKT signalling pathways in human DLBCL cells. An in vivo experiment exhibited that CPI-0610 decreased the primary tumour growth of the DLBCL xenograft model. Furthermore, the use of CPI-0610 in combination with suberoylanilide hydroxamic acid exhibited a specific synergistic effect in inducing apoptosis through the regulation of STAT3 and p38.

Conclusion::

Targeting BET may be an effective therapeutic strategy and potentiated by a combination with histone deacetylase inhibition in DLBCL.

06 Feb 2025·BLOOD

Preclinical efficacy of CDK7 inhibitor–based combinations against myeloproliferative neoplasms transformed to AML

Article

Author: Loghavi, Sanam ; Philip, Kevin ; Masarova, Lucia ; Hou, Hanxi ; DiNardo, Courtney ; Birdwell, Christine E. ; Dunbar, Andrew ; Matthews, Alicia ; Pemmaraju, Naveen ; Malovannaya, Anna ; Fiskus, Warren ; Bose, Prithviraj ; Davis, John A. ; Flores, Lauren B. ; Alhamadani, Noor ; Das, Kaberi ; Lin, Katie ; Rampal, Raajit K. ; Bhalla, Kapil N. ; Jain, Antrix ; Su, Xiaoping ; Mill, Christopher P. ; Manshouri, Taghi

Abstract:

Rising blast percentage or secondary acute myeloid leukemia (sAML) transformation in myeloproliferative neoplasms (MPNs) leads to JAK1/2 inhibitor (JAKi) therapy resistance and poor survival. Here, we demonstrate that treatment with the CDK7 inhibitor (CDK7i) SY-5609 depletes phenotypically characterized post-MPN sAML stem/progenitor cells. In cultured post-MPN sAML SET2, HEL and patient-derived (PD) post-MPN sAML cells, SY-5609 treatment inhibited growth and induced lethality while sparing normal cells. RNA-sequencing analysis after SY-5609 treatment reduced mRNA expression of MYC, MYB, CDK4/6, PIM1, and CCND1 but increased expression of CDKN1A and BCL2L1. Mass spectrometry of SY-5609–treated MPN-sAML cells also reduced c-Myc, c-Myb, PIM1, and CDK4/6 but increased p21, caspase-9, and BAD protein levels. CRISPR-mediated CDK7 depletion also reduced cell viability of HEL cells. Cytometry by time of flight (CyTOF) analysis of SY-5609–treated PD post-MPN sAML stem/progenitor cells showed reduced c-Myc, CDK6, and PU.1 but increased protein levels of CD11b, p21, and cleaved caspase-3. Cotreatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2, and PD post-MPN sAML cells. A CRISPR screen in sAML cells revealed BRD4, CBP, and p300 as codependencies with CDK7i. Accordingly, cotreatment with SY-5609 and the bromodomain and extra-terminal protein inhibitor (BETi) OTX015 or pelabresib or the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared with each agent alone, cotreatment with SY-5609 and OTX015 reduced sAML burden and improved survival without host toxicity. These findings demonstrate promising preclinical activity of CDK7i-based combinations with BETi or CBP/p300 inhibitor against advanced MPNs, including post-MPN sAML.

01 May 2024·American journal of hematology

JAK inhibitor treatment‐resistant splenomegaly before transplantation in myelofibrosis: Splenectomy or radiotherapy?

Communications

Author: Tefferi, Ayalew ; Finazzi, Maria Chiara ; Rambaldi, Alessandro

A review.A review discussing JAK inhibitor treatment-resistant splenomegaly before transplantation in myelofibrosis.It also discusses the possibility of using alternative JAK inhibitors, such as fedratinib, or emerging new therapies that might enhance the spleen effect from ruxolitinib (e.g., pelabresib), thus providing yet other pretransplant treatment options for massive splenomegaly.

News (Medical) associated with Pelabresib

22 Jan 2025

·www.fiercepharma.com

JPM25: Incyte plans to turn 'a lot of cards' in 2025 as CEO eyes 2 types of deals

For dealmaking purposes, Incyte CEO Hervé Hoppenot said the company is currently only looking for commercial products or early-stage assets with novel technologies. During his presentation at the J.P. Morgan Healthcare Conference last week, Incyte CEO Hervé Hoppenot took investors on a whirlwind tour of 18 events that could take place throughout 2025.“We will be turning a lot of these cards during the year,” Hoppenot said during an interview with Fierce Pharma on the sidelines of JPM.Among the 18 events, Incyte is preparing for four launches across cancer and immunology, and it’s gearing up for four pivotal readouts, including two that investors are watching closely. Overall, Hoppenot said he’s looking forward to an eventful 2025 as Incyte reels from some bad news in its pipeline and as the company remains open to two specific types of deals. Expanding commercial products Together with partner Syndax Pharmaceuticals, Incyte in August won the FDA’s approval for Niktimvo in third-line chronic graft-versus-host disease. Trying to get a smaller vial approved, the partners are aiming to embark on an official rollout soon.Also in immunology, Incyte is trying to build on the successful launch of Opzelura cream, with a proposed pediatric expansion in atopic dermatitis submitted to the FDA and a phase 3 prurigo nodularis readout expected in the first half of 2025.On the oncology side of the business, the firm is counting on two potential FDA nods in the second half of the year—one for CD19 antibody Monjuvi in follicular lymphoma and the other for PD-1 inhibitor Zynyz in first line squamous cell anal carcinoma.Incyte had originally tried to get Zynyz approved in previously treated anal cancer, but its effort was shot down by the FDA in 2021 after a negative review from an advisory committee.This time, Hoppenot argued Zynyz’s data set in the first-line setting is “as clear as it could be,” adding that the company doesn’t anticipate any regulatory hurdles. In a first-in-class win, Zynyz and chemotherapy slashed the risk of progression or death by 37% compared with chemo alone in first-line anal cancer in the phase 3 POD1UM-303 trial.Incyte last year also reported a positive outcome from the POD1UM-304 study, which pitted a Zynyz-chemo combo against solo chemo in first-line non-small cell lung cancer. Given the chemo comparator arm and how PD-1 drugs such as Merck & Co.’s Keytruda have already become the standard of care, the FDA will probably not consider Incyte’s study sufficient to support an approval.Incyte is still speaking with the FDA about the indication, and Hoppenot acknowledged that the agency has “been always asking questions about the relevance of having one more of the same thing.”But the company’s main business plan for the PD-1 latecomer is not necessarily in the U.S. market. Instead of the drug becoming a big contributor to the top line, Hoppenot views Zynyz as an “opportunistic product” for parts of the world where first-line access to PD-1 drugs isn’t established. To seek easy green lights in places such as the Middle East and Brazil, Incyte will first need a reference approval. If not from the FDA, such a nod could come from authorities in the U.K. or Switzerland, Hoppenot explained. This strategy of using a reference approval to move into emerging markets is also being used by many Chinese PD-1 developers. The biggest opportunity that could emerge from Incyte’s oncology department in 2025 is an upcoming phase 3 readout for Monjuvi in first-line diffuse large B-cell lymphoma (DLBCL). While this is a large indication, Incyte is forecasting a U.S. market opportunity below $1 billion, partly because of competition from Roche’s recent entrant, the antibody-drug conjugate Polivy.After Roche’s hard-fought first-line approval for the Polivy-R-CHP combination regimen in 2023, around 20% of new DLBCL patients are starting on the regimen, Hoppenot noted.Meanwhile, Incyte’s phase 3 frontMIND study is testing the addition of Monjuvi to the R-CHOP regimen versus R-CHOP itself. Hoppenot said he’s optimistic about a positive readout given the strong performance of the CD19-CD20 combination approach in follicular lymphoma in the phase 3 inMIND trial. Advancing a ‘full’ portfolio despite setbacks In keeping with the cards theme, Incyte has faced its share of difficult poker hands lately. And the CEO continues to field investor questions about life after Jakafi’s expected loss of exclusivity in the U.S. in 2028.The most disappointing development the company has faced is perhaps a preclinical toxicology discovery from INCB000262, the crown jewel of Incyte’s $750 million buyout of Escient Pharmaceuticals. As a result of the safety signal, clinical development of the MRGPRX2 inhibitor was put on hold in November, less than six months after the acquisition.While Incyte is still trying to elucidate the problem and has not decided whether it needs to turn to a backup molecule, “the probability of moving forward is relatively low,” Hoppenot explained.“You can acquire an asset that is well understood and that will cost you billions, or you acquire an early asset, like what we did, and it will cost you millions instead," Hoppenot said. “There is no way you can predict it, and that’s part of the trade-off,” the CEO added.Another safety cloud forming over Incyte’s pipeline pertains to the BET inhibitor class. Novartis recently postponed potential regulatory filings for its BET inhibitor candidate pelabresib, which was acquired in its $2.9 billion MorphoSys takeout, because of malignant transformations identified during clinical testing.Updated MANIFEST-2 trial data presented in December showed that among myelofibrosis patients who received the combination of Jakafi and pelabresib, 6.1% developed acute myeloid leukemia (AML). The number compared with 4.2% for those who took Jakafi alone.In a phase 1 study, Incyte spotted a rate of AML transformations of 4.9% for its BET inhibitor INCB057643 among patients with high-risk myelodysplastic syndromes or myelofibrosis. Patients with those blood disorders are naturally at risk of developing AML, Hoppenot noted, arguing that it’s too early to conclude there is a classwide problem for BET inhibitors. The only way to know for sure is through a randomized study with a comparator arm.Unlike Novartis’ front-line study, Incyte is launching a phase 3 trial for its BET inhibitor as a monotherapy in the post-Jakafi setting. The company has not decided whether it will run a similar BET-Jakafi combo trial in the first line “because there is a portfolio question for us with two other projects,” Hoppenot said, pointing to the company's early-stage mutant CALR antibody and JAK2V617F inhibitor.Depending on phase 1 readouts for those candidates, Incyte will have the luxury of deciding whether it makes sense to move a BET inhibitor into the first-line setting, the CEO explained.An opportunity in hidradenitis suppurativa Despite questions around the BET class and the Escient buy, Hoppenot argued Incyte’s portfolio is currently “full.” Investors are also waiting with bated breadth to see phase 3 results for povorcitinib in hidradenitis suppurativa (HS) in the first quarter of 2025.HS represents a historically underserved population. For years, AbbVie’s Humira served as the only treatment option until the recent approvals of Novartis’ Cosentyx and UCB’s Bimzelx, Leerink Partners analysts said in a recent note.Studies suggest the disease affects about 4% of the population, according to Leerink. If successful, Incyte's povorcitinib could become the first oral drug for the indication. HS could represent a $10 billion annual market opportunity that's “capable of supporting multiple blockbuster agents,” according to the Leerink analysts. “We know in dermatology, there are a lot of patients who would rather be treated with the pills than with an injection,” Hoppenot noted, pointing to how Amgen’s Otezla has been successful in psoriasis even though it’s considered less efficacious than biologics.What Incyte is gunning for is biologiclike efficacy in an oral drug, Hoppenot said of povorcitinib.The chief executive didn’t directly answer a question about whether Incyte would need to turn to M&A if povorcitinib were to fail in HS. For now, with a “full” portfolio, Incyte is only considering two types of deals, according to Hoppenot.“If we look for something, it would be mostly new technologies that we don’t have. So, early-stage, exotic stuff,” Hoppenot said, “or on the opposite end, commercial product, because that will be contributing to the top line immediately.”The company will also stick to its interest areas, namely cancer and dermatology, he said.

Phase 3Clinical ResultDrug ApprovalPhase 1Acquisition

25 Nov 2024

·www.globenewswire.com

Novartis highlights new 96-week results from Phase III Scemblix® ASC4FIRST trial at ASH and late-breaking analysis from Phase III Kisqali® NATALEE trial at SABCS

Longer-term 96-week results from Scemblix® ASC4FIRST Phase III study in first-line Ph+ CML-CP to be presented following recent FDA approval based on 48-week data Late-breaking Kisqali®* 4-year analysis on distant disease-free survival in key subgroups with HR+/HER2- early breast cancer from Phase III NATALEE trial also to be presentedPipeline updates demonstrate advancement in research and development programs in hematologic diseases and cancers Basel, November 25, 2024 – Novartis will present data from more than 65 abstracts, including investigator-initiated trials at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition and the 2024 San Antonio Breast Cancer Symposium® (SABCS). “By prioritizing research in areas of greatest medical need and focusing on earlier stages of disease, we aim to change the treatment paradigm for people who require additional treatment options,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. “The new data being presented at ASH and SABCS underscore our commitment to patients with cancer or blood disorders and follow new, expanded indications for Scemblix and Kisqali along with recent updates in national treatment guidelines." In addition to late-breaking data, Novartis will host an art gallery-style exhibit at SABCS featuring personal letters and stories written by people impacted by breast cancer, sharing their raw, authentic perspectives on aspects of the breast cancer journey. These letters and stories aim to uplift patients, encourage reflection, and demonstrate strength and unity among the breast cancer community. Key abstracts accepted by ASH include: Medicine or Disease State      Abstract Title      Abstract Number/ Presentation Details       Scemblix®Asciminib (ASC) Demonstrates Favorable Safety and Tolerability Compared with Each Investigator-Selected Tyrosine Kinase Inhibitor (IS TKI) in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Pivotal Phase 3 ASC4FIRST Study Abstract #475Oral PresentationSunday, December 89:30 – 11:00 AM PTScemblix   Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI) Abstract #479Oral PresentationSunday, December 89:30 – 11:00 AM PTScemblix Asciminib Shows High Efficacy and Favorable Tolerability at 80 Mg Once Daily and 40 Mg Twice Daily in Patients with Chronic Phase Chronic Myelogenous Leukemia Previously Treated with 2 or More Tyrosine Kinase Inhibitors: Primary Analysis from the ASC4OPT Study Abstract #4526Poster PresentationMonday, December 96:00 – 8:00 PM PTScemblix Treatment with Asciminib as a Second Line after One Prior Tyrosine Kinase Inhibitor (TKI) in Patients with Chronic-Phase Chronic Myeloid Leukemia (CML-CP)– a Chart Review Study in the United States Abstract #3812Poster PresentationSunday, December 86:00 – 8:00 PM PTIanalumab (VAY736)A Phase 2 Study of Ianalumab in Patients with Primary Immune Thrombocytopenia Previously Treated with at Least Two Lines of Therapy: Interim Results from VAYHIT3 Abstract #710Oral PresentationMonday, December 910:30 AM – 12:00 PM PTRapcabtagene autoleucel (YTB323)Rapcabtagene Autoleucel (YTB323) in Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Phase II Trial Clinical Update Abstract #67Oral PresentationSaturday, December 79:30 – 11:00 AM PTFabhalta®Oral Iptacopan Monotherapy Leads to Long-Term Improvements in Patient (Pt)-Reported Health-Related Quality of Life (HRQoL) and Investigator-Assessed Signs and Symptoms of Paroxysmal Nocturnal Hemoglobinuria (PNH): 48-Week (Wk) Results from the Phase III APPLY-PNH and APPOINT-PNH Trials Abstract #4079Poster PresentationMonday, December 96:00 – 8:00 PM PTFabhalta The Effect of Oral Iptacopan Monotherapy on Hematological Parameters in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Is Consistent Regardless of the Type of Prior Anti-C5 Treatment Received: A Post Hoc Analysis of 24-Week Data from the Randomized Phase III APPLY-PNH Trial Abstract #4087Poster PresentationMonday, December 96:00 – 8:00 PM PTFabhalta Baseline Characteristics of Individuals with Paroxysmal Nocturnal Hemoglobinuria in an App-Based Home-Reported Outcomes Study to Evaluate Disease Burden Abstract #2327Poster PresentationSaturday, December 75:30 – 7:30 PM PTPelabresib (CPI-0610)Updated Results from the Phase 3 Manifest-2 Study of Pelabresib in Combination with Ruxolitinib for Janus Kinase Inhibitor–Naïve Patients with MyelofibrosisAbstract #3178Poster PresentationSunday, December 86:00 PM - 8:00 PM PT Key abstracts accepted by SABCS include: Medicine or Disease State      Abstract Title      Abstract Number/ Presentation Details       Kisqali® (ribociclib)* Distant disease-free survival (DDFS) across key subgroups from the phase 3 NATALEE trial of ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) in patients with HR+/HER2- early breast cancer (EBC) Abstract #P4-09-22Poster SessionThursday, December 125:30 – 7:30 PM CST Kisqali     Impact of ribociclib dose reduction on efficacy in patients with hormone receptor– positive/human epidermal growth factor receptor 2–negative (HR+/HER2-) early breast cancer (EBC) in NATALEE Abstract #P1-11-16Poster Session Wednesday, December 1112:30 – 2:00 PM CSTKisqali Risk of recurrence in real-world (RW) NATALEE- and monarchE-eligible populations of patients with HR+/HER2- early breast cancer (EBC) in an electronic health record (EHR)-derived database Abstract #P2-12-02Poster SessionWednesday, December 115:30 – 7:00 PM CST Kisqali Tolerability of First-Line (1L) Treatment (tx) With Ribociclib (RIB) for Metastatic Breast Cancer (MBC) Using 2 Large US Data Sources Abstract #P3-10-14Poster SessionThursday, December 1212:30 – 2:00 PM CST Kisqali Impact of body mass index (BMI) on the safety and efficacy of ribociclib (RIB) in patients (pts) with HR+/HER2- advanced breast cancer (ABC): pooled analysis of the MONALEESA (ML)-2, -3, and -7 trials Abstract #P2-09-20Poster SessionWednesday, December 115:30 – 7:00 PM CST Kisqali First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in clinically aggressive HR+/HER2- advanced breast cancer (ABC): a subgroup analysis of RIGHT Choice by intrinsic subtype & gene & signature expression Abstract #PS2-06Poster PresentationThursday, December 127:00 – 8:30 AM CST Product Information     For full prescribing information, including approved indications and important safety information about marketed products, please visit https://www.novartis.com/about/products. DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this 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. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. # # # * Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals. Novartis Media RelationsE-mail: media.relations@novartis.com Central North America Anja von Treskow+41 79 392 9697Michael Meo+1 862 274 5414Anna Schäfers+41 79 801 7267 SwitzerlandSatoshi Sugimoto +41 79 619 2035 Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com Central North America Isabella Zinck+41 61 324 7188Sloan Simpson+1 862 345 4440Nicole Zinsli-Somm+41 61 324 3809Jonathan Graham+1 201 602 9921Imke Kappes+41 61 324 8269Parag Mahanti+1 973 876 4912

Phase 3Clinical ResultPhase 2ASH

21 Nov 2024

·endpts.com

Novartis seeks more bolt-on deals as it purchases neuro startup for up to $1.1B

Novartis is buying gene therapy and neuroscience biotech Kate Therapeutics in a deal worth $1.1 billion in upfront and milestone payments, the Swiss pharma confirmed to Endpoints News on Thursday. And Novartis is not done yet. It is still on the lookout for bolt-on M&A opportunities — but don’t expect them to go higher than $3 billion. “That’s not that we couldn’t do a little bit bigger, but that’s the majority of the available target companies, if you will,” Novartis CFO Harry Kirsch told the media ahead of its investor event in London on Thursday. CEO Vas Narasimhan added that a lot of M&A from the recent past has been in the $1 billion to $2 billion range, pointing to its acquisitions of Mariana Oncology and KateTx. Over the past eight years, it made $5 billion to $10 billion deals only “occasionally” because of valuation considerations and “financial discipline,” he added. Novartis will take on KateTx’s pipeline of preclinical candidates in Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy and myotonic dystrophy type 1. The San Diego biotech’s gene therapy tech features adeno-associated virus capsids that deliver their payloads into specific tissues to avoid off-target issues such as hepatic side effects. In June 2023, it said that it was partnering with Astellas on a neuromuscular disease called X-linked myotubular myopathy. Novartis revealed its purchase of KateTx ahead of its Meet Novartis Management event in London that was intended to reassure investors its pure-play strategy is bearing fruit now and in the next several years. A key part of its growth strategy is more M&A as “replacement power,” with the company facing the loss of exclusivity for key drugs such as Entresto , Kirsch said. When asked if changes to the Federal Trade Commission could lead to Novartis raising its M&A budget, Narasimhan said the FTC is not a major driver of its decisions. As a part of its reorg, the company zeroed in on four therapeutic spaces: cardiovascular-renal-metabolic, immunology, neuroscience and oncology. “Preclinical, Phase 1, Phase 2 area — that’s the opportunity where we can step in” and Novartis can add value to the acquired company, Narasimhan said, adding that it’s challenging to “find synergies, harder to justify” with later-stage candidates. Narasimhan said that when it bought MorphoSys for $2.9 billion, its lead oncology candidate , pelabresib, was in an ongoing Phase 3 trial. “We saw the opportunity in an area of myelofibrosis that we’ve been in for a long period of time, and we took a bet on an ongoing clinical trial,” he said, adding that if it had waited for the late-stage readout, the purchase price would have been “double at least.” But that bet on MorphoSys led to the company taking an $800 million impairment hit just months after the deal closed due to emergent malignancies. “In this case, it didn’t go our way,” he said, nonetheless noting the company’s overall M&A track record . As for pelabresib, the company’s next update should come in the second half of next year. Narasimhan said it is monitoring patients until the middle of next year. “We are also planning to conduct additional studies to look at certain subpopulations of myelofibrosis patients where pelabresib could have a better benefit-risk profile. So I think all of that will take us at least until 2027 — it might take longer, depending on the safety topic,“ he added.

AcquisitionPhase 3Phase 2Gene TherapyPhase 1

100 Deals associated with Pelabresib

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Leukemia	Phase 3	United States	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Leukemia	Phase 3	Belgium	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Leukemia	Phase 3	Italy	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Leukemia	Phase 3	Netherlands	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Leukemia	Phase 3	United Kingdom	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	United States	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	Belgium	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	Italy	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	Netherlands	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	United Kingdom	Constellation Pharmaceuticals, Inc.	13 Aug 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04603495 (MANIFEST-2, CTgov)	Phase 3	Post-essential thrombocythemia myelofibrosis \| Post-polycythemia vera myelofibrosis \| Primary Myelofibrosis	430	Ruxolitinib+Pelabresib (Pelabresib + Ruxolitinib)	yipzmrkxxp = uanaqkzisb kcfhmcrems (sixbtgurqr, yafjwnyvkb - wgavfqychy) View more	-	28 Oct 2024
				Placebo+Ruxolitinib (Placebo + Ruxolitinib)	yipzmrkxxp = suaasasvpx kcfhmcrems (sixbtgurqr, ujcxtkkled - yhwhojfqjg) View more
SOHO2024	Not Applicable	Myelofibrosis	-	Pelabresib+ruxolitinib	mgmnjovprm(ctvgdcjbmb) = 43.9% vs 54.7% omuewqpdoi (aiiavglxrc ) View more	-	04 Sep 2024
				Placebo+ruxolitinib
NCT04603495 (MANIFEST-2, ASCO2024) Manual	Phase 3	Myelofibrosis	430	Pelabresib + Ruxolitinib	ftksjzvgsd(czwggrsddf) = fglesxrheg fwlyinywaw (egendutvgs ) View more	Positive	24 May 2024
				Placebo + Ruxolitinib	ftksjzvgsd(czwggrsddf) = lxvdaerotm fwlyinywaw (egendutvgs ) View more
NCT04603495 (MANIFEST-2, EHA2024) Manual	Phase 3	Myelofibrosis JAK2	-	Pelabresib+Ruxolitinib	pvbwyaclpz(qlemdizomu) = vgtycnuusk oaurancubl (skugqtmywb, -36.5 to -31.1) View more	Positive	14 May 2024
				Placebo+Ruxolitinib	pvbwyaclpz(qlemdizomu) = gcpdehhvac oaurancubl (skugqtmywb, -23.7 to -17.9) View more
NCT02158858 (MANIFEST, Pubmed) Manual	Phase 1	Myeloid Tumor Protein Expression Markers	44	Pelabresib	vvvqribgso(dhaqdiufkw) = nausea, decreased appetite, and fatigue rdrkcufzve (qfxnvgkajq ) View more	Positive	23 Jan 2024
				Pelabresib (acute leukemia)
NCT04603495 (MANIFEST-2, Corporate Publications) Manual	Phase 3	Primary Myelofibrosis	430	Pelabresib + Ruxolitinib	vfueoakfvm(gnwrrnelsb) = nhkebpiqoe gazxdlrzmd (kvwezmncdj ) Met View more	Positive	20 Nov 2023
				Placebo + Ruxolitinib	vfueoakfvm(gnwrrnelsb) = zbefotsxzt gazxdlrzmd (kvwezmncdj ) Met View more
NCT02158858 (MANIFEST, EHA2023)	Phase 2	Acute Myeloid Leukemia \| Thrombocytopenia \| Hematologic Neoplasms ... View more	84	PELA + RUX	ikwhszbmrl(hzjvhhohwt) = yhejwryxai vqtjzphvyf (ffqsditbkj ) View more	-	08 Jun 2023
NCT02158858 (MANIFEST, EHA2023)	Phase 2	Primary Myelofibrosis Add-on	87	PELA + RUX	zjsjwpefcp(vhisiwqzbq) = ikkjofujiw qmnstqifpk (pizzgjonsh ) View more	-	08 Jun 2023
NCT02158858 (ASCO 12023 \| ASCO 22023) Manual	Phase 1/2	Thrombocythemia, Essential	20	Pelabresib 225mg	gilywzudqo(iqcgrtahdq) = elkpsmivjl imynijpqzz (adbfaclyos ) View more	Positive	31 May 2023
NCT02158858 (MANIFEST, Pubmed)	Phase 2	Primary Myelofibrosis	84	Pelabresib and Ruxolitinib	ddimxkjqgg(gxlxigmmfd) = cdvpwszjls zrjylctlig (lcrkohuhnf ) View more	-	07 Mar 2023

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