A Phase 2 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed or Refractory CD10-Negative Diffuse-Large B-Cell Lymphoma (DLBCL) and High-Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements (HGBCL-DH-BCL2)

This phase II trial tests how well venetoclax, ibrutinib, prednisone, obinutuzumab, and Revlimid® (ViPOR) works in treating patients with CD10 negative diffuse large B-cell lymphoma (DLBCL) and high-grade lymphoma with MYC and BCL2 rearrangements that has come back after a period of improvement (relapsed) and/or that has not responded to previous treatment (refractory). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ibrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers at abnormal levels. This may help keep cancer cells from growing and spreading. Anti-inflammatory drugs, such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Obinutuzumab, a monoclonal antibody, binds to a protein called CD20, which is found on B cells and some types of leukemia and lymphoma cells. Obinutuzumab may block CD20 and help the immune system kill cancer cells. Revlimid, a type of anti-angiogenesis agent and a type of immunomodulating agent, may help the immune system kill abnormal blood cells or cancer cells. It may also prevent the growth of new blood vessels that cancers need to grow. ViPOR may be an effective treatment option for patients with relapsed and/or refractory CD10 negative DLBCL and high-grade B-cell lymphoma with MYC and BCL2 rearrangements.

Start Date17 Jan 2025

Sponsor / Collaborator

National Cancer Institute

NCT06271616 / Not yet recruitingPhase 2IIT

A Phase II Study of Ibrutinib as Prophylaxis for Chronic Graft-Versus-Host Disease (GVHD) in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation (Allo-HCT)

This phase II trial tests how well ibrutinib works in preventing chronic graft-versus-host disease (GVHD) in patients undergoing donor (allogeneic) hematopoietic cell transplantation (HCT). An allogeneic hematopoietic cell transplantation (allo-HCT) is a treatment in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical donor. When healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets. However, sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). Giving ibrutinib after the transplant may stop that from happening. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking a protein in the blood called Bruton's tyrosine kinase (BTK). By blocking BTK, ibrutinib inhibits certain immune cells that play a role in cGVHD. Giving ibrutinib after an allo-HCT may prevent the development of chronic GVHD.

Start Date01 Nov 2024

Sponsor / Collaborator

Mayo Clinic

NCT06536049 / Not yet recruitingPhase 1/2IIT

Phase Ib/II Trial of Epcoritamab Plus Ibrutinib in Patients With Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma

This phase Ib/II trial evaluates the safety, optimal dose, and efficacy of the combination of epcoritamab and ibrutinib in treating patients with aggressive B-cell non-Hodgkin lymphoma that has come back (relapsed) or responded to previous treatment (refractory). Epcoritamab, a bispecific antibody, binds to two different types of receptors (proteins present on the cell surface) at the same time. The two receptors that epcoritamab binds to are called CD3 and CD20. CD3 is found on T cells, which are important cells of the immune system that help fight cancer and infections. CD20 is found on the surface of most types of aggressive B-cell non-Hodgkin lymphoma cells. By binding to both CD3 and CD20, epcoritamab brings the two cells close together so the T cells can fight and kill the lymphoma B cells. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, binds to a protein on B cells, a type of white blood cell from which the lymphoma developed. By doing this it decreases the ability of the lymphoma B cells to survive and grow. Ibrutinib may also improve the health (or fitness) of T cells thus making epcoritamab safer and/or more effective.

Start Date31 Oct 2024

Sponsor / Collaborator

Ohio State University Comprehensive Cancer Center

[+2]

100 Clinical Results associated with Ibrutinib

100 Translational Medicine associated with Ibrutinib

100 Patents (Medical) associated with Ibrutinib

3,797

Literatures (Medical) associated with Ibrutinib

31 Dec 2024·CNS Oncology

Prolonged remission with ibrutinib maintenance therapy following radiation in a patient with relapsed primary CNS lymphoma

Article

Author: Kong, Xiao-Tang ; Fu, Dan Beverly ; A Bota, Daniela ; Du, Steven

Background: Treatment for refractory or relapsed primary CNS lymphoma (r/r PCNSL) is challenging. Salvage whole-brain radiation therapy (WBRT) is an option but has a short duration of disease control, so additional treatment modalities are warranted. Case: A 75-year-old female with r/r PCNSL who had multiple progressions after multiple lines of treatment underwent salvage WBRT. The patient received ibrutinib, a Bruton's tyrosine kinase inhibitor, as maintenance therapy for 18 months following WBRT with the intention of increasing survival duration after salvage WBRT. She survived 81 months from diagnosis, including 57 months after completion of WBRT. Conclusion: This case presentation describes the experience of using ibrutinib as maintenance therapy in treating r/r PCNSL after salvage WBRT.

01 Dec 2024·eNeurologicalSci

Paraneoplastic myelitis associated with Waldenström macroglobulinemia responsive to treatment with ibrutinib – venetoclax: A case report

Article

Author: Galetta, Kristin M ; Galetta, Kristin M. ; Bhattacharyya, Shamik ; Castillo, Jorge J. ; Narasimhan, Sathya ; Castillo, Jorge J

Waldenström macroglobulinemia (WM) is a B-cell lymphoproliferative malignancy characterized by IgM paraproteinemia and presence of lymphoplasmacytic cells in the bone marrow. Isolated longitudinally extensive transverse myelitis (LETM) is a rare manifestation of WM. We report a rare case of paraneoplastic LETM in a 68-year-old male with treatment-naïve WM (MYD88 L265P mutation in bone marrow aspirate), who responded to ibrutinib and venetoclax therapy. Our patient presented with a two-month history of unsteadiness, tingling, and numbness in both hands and feet, that progressed to bilateral leg and arm weakness. Based on radiographic findings, a diagnosis of paraneoplastic LETM was made and he was treated acutely with IV methylprednisolone followed by a quick oral prednisone taper. However, he subsequently relapsed and symptomatically worsened while on rituximab therapy. Accounting for worsening anemia, our patient was enrolled in a Phase II trial evaluating the effects of ibrutinib-venetoclax therapy in treatment naïve WM. After three months of study therapy, he had a complete response of myelopathy symptoms and MRI lesions. Our observation of sustained disease response in this patient may support a role for concurrent BTK and BCL2 inhibition in paraneoplastic myelitis associated with B-cell lymphoproliferative disorders. However, this observation needs to be validated in larger cohort studies and potentially in clinical trials if further data are supportive.

01 Dec 2024·Pediatric Blood & Cancer

Successful ibrutinib treatment for pulmonary involvement in a post‐transplant patient with inherited bone marrow failure syndrome and very short telomeres

Letter

Author: Okura, Eri ; Maruyama, Yuta ; Tanaka, Miyuki ; Nakazawa, Yozo ; Saito, Shoji ; Furui, Yu ; Hirabayashi, Koichi

489

News (Medical) associated with Ibrutinib

30 Oct 2024

·www.prnewswire.com

AbbVie Reports Third-Quarter 2024 Financial Results

Reports Third-Quarter Diluted EPS of $0.88 on a GAAP Basis, a Decrease of 12.0 Percent; Adjusted Diluted EPS of $3.00, an Increase of 1.7 Percent; These Results Include an Unfavorable Impact of $0.04 Per Share Related to Acquired IPR&D and Milestones Expense Delivers Third-Quarter Net Revenues of $14.460 Billion, an Increase of 3.8 Percent on a Reported Basis or 4.9 Percent on an Operational Basis Third-Quarter Global Net Revenues from the Immunology Portfolio Were $7.046 Billion, an Increase of 3.9 Percent on a Reported Basis, or 4.8 Percent on an Operational Basis; Global Humira Net Revenues Were $2.227 Billion; Global Skyrizi Net Revenues Were $3.205 Billion; Global Rinvoq Net Revenues Were $1.614 Billion Third-Quarter Global Net Revenues from the Oncology Portfolio Were $1.687 Billion, an Increase of 11.6 Percent on a Reported Basis, or 13.0 Percent on an Operational Basis; Global Imbruvica Net Revenues Were $828 Million; Global Venclexta Net Revenues Were $677 Million Third-Quarter Global Net Revenues from the Neuroscience Portfolio Were $2.363 Billion, an Increase of 15.6 Percent on a Reported Basis, or 16.0 Percent on an Operational Basis; Global Botox Therapeutic Net Revenues Were $848 Million; Global Vraylar Net Revenues Were $875 Million; Combined Global Ubrelvy and Qulipta Net Revenues Were $445 Million Third-Quarter Global Net Revenues from the Aesthetics Portfolio Were $1.239 Billion, a Decrease of 0.1 Percent on a Reported Basis, or an Increase of 1.8 Percent on an Operational Basis; Global Botox Cosmetic Net Revenues Were $671 Million; Global Juvederm Net Revenues Were $258 Million Successfully Completed Acquisition of Cerevel, Adding Pipeline of Highly Complementary Assets to AbbVie's Existing Neuroscience Portfolio Raises 2024 Adjusted Diluted EPS Guidance Range from $10.67 - $10.87 to $10.90 - $10.94, which Includes an Unfavorable Impact of $0.64 Per Share Related to Acquired IPR&D and Milestones Expense Incurred Year-To-Date Through the Third Quarter 2024 Announces 2025 Dividend Increase of 5.8 Percent, Beginning with Dividend Payable in February 2025 NORTH CHICAGO, Ill., Oct. 30, 2024 /PRNewswire/ -- AbbVie (NYSE:ABBV) announced financial results for the third quarter ended September 30, 2024. "We delivered another quarter of strong commercial execution and significant pipeline progress," said Robert A. Michael, chief executive officer, AbbVie. "Based upon the momentum of AbbVie's business and our confidence in the long-term growth outlook, we are once again raising our full-year guidance and are increasing our quarterly dividend." Third -Quarter Results Worldwide net revenues were $14.460 billion, an increase of 3.8 percent on a reported basis, or 4.9 percent on an operational basis. Global net revenues from the immunology portfolio were $7.046 billion, an increase of 3.9 percent on a reported basis, or 4.8 percent on an operational basis. Global Humira net revenues of $2.227 billion decreased 37.2 percent on a reported basis, or 36.5 percent on an operational basis. U.S. Humira net revenues were $1.765 billion, a decrease of 41.6 percent. Internationally, Humira net revenues were $462 million, a decrease of 12.4 percent on a reported basis, or 7.8 percent on an operational basis. Global Skyrizi net revenues were $3.205 billion, an increase of 50.8 percent on a reported basis, or 51.5 percent on an operational basis. Global Rinvoq net revenues were $1.614 billion, an increase of 45.3 percent on a reported basis, or 47.4 percent on an operational basis. Global net revenues from the oncology portfolio were $1.687 billion, an increase of 11.6 percent on a reported basis, or 13.0 percent on an operational basis. Global Imbruvica net revenues were $828 million, a decrease of 8.8 percent, with U.S. net revenues of $618 million and international profit sharing of $210 million. Global Venclexta net revenues were $677 million, an increase of 14.8 percent on a reported basis, or 18.2 percent on an operational basis. Global Elahere net revenues were $139 million. Global net revenues from the neuroscience portfolio were $2.363 billion, an increase of 15.6 percent on a reported basis, or 16.0 percent on an operational basis. Global Botox Therapeutic net revenues were $848 million, an increase of 13.4 percent on a reported basis, or 14.4 percent on an operational basis. Global Vraylar net revenues were $875 million, an increase of 16.6 percent. Global Ubrelvy net revenues were $269 million, an increase of 15.3 percent. Global Qulipta net revenues were $176 million, an increase of 33.6 percent. Global net revenues from the aesthetics portfolio were $1.239 billion, a decrease of 0.1 percent on a reported basis, or an increase of 1.8 percent on an operational basis. Global Botox Cosmetic net revenues were $671 million, an increase of 8.2 percent on a reported basis, or 9.9 percent on an operational basis. Global Juvederm net revenues were $258 million, a decrease of 19.7 percent on a reported basis, or 16.9 percent on an operational basis. On a GAAP basis, the gross margin ratio in the third quarter was 70.9 percent. The adjusted gross margin ratio was 84.4 percent. On a GAAP basis, selling, general and administrative (SG&A) expense was 29.1 percent of net revenues. The adjusted SG&A expense was 23.0 percent of net revenues. On a GAAP basis, research and development (R&D) expense was 14.7 percent of net revenues. The adjusted R&D expense was 14.2 percent of net revenues. Acquired IPR&D and milestones expense was 0.6 percent of net revenues. On a GAAP basis, the operating margin in the third quarter was 26.5 percent. The adjusted operating margin was 46.7 percent. Net interest expense was $591 million. On a GAAP basis, the tax rate in the quarter was 25.0 percent. The adjusted tax rate was 16.2 percent. Diluted EPS in the third quarter was $0.88 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $3.00. These results include an unfavorable impact of $0.04 per share related to acquired IPR&D and milestones expense. Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year's foreign exchange rates. Recent Events AbbVie announced that it completed its acquisition of Cerevel, adding a pipeline of highly complementary assets to AbbVie's existing neuroscience portfolio. Cerevel's pipeline includes emraclidine, a potential best-in-class, next-generation antipsychotic, that is being studied for the treatment of schizophrenia; tavapadon, a first-in-class dopamine D1/D5 selective partial agonist for the management of Parkinson's disease (PD); as well as CVL-354, a potential best-in-class kappa opioid receptor (KOR) antagonist being studied for the treatment of major depressive disorder (MDD). Cerevel is a strong strategic fit for AbbVie and has potential to meaningfully impact revenue into the next decade. AbbVie announced positive topline results from its pivotal Phase 3 TEMPO-1 trial evaluating tavapadon as a fixed-dose monotherapy treatment in early PD. In the study, tavapadon met the primary endpoint, demonstrating a statistically significant improvement from baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score at week 26. Tavapadon also met the key secondary endpoint, demonstrating statistically significant improvement from baseline in the MDS-UPDRS Part II score. Full results from the TEMPO-1 study will be submitted for presentation at future medical meetings and used to support regulatory submissions of tavapadon as a treatment for PD. Topline results from TEMPO-2, the Phase 3 flexible-dose monotherapy trial for tavapadon, are expected by the end of 2024. AbbVie announced the U.S. Food and Drug Administration (FDA) approved Vyalev (foscarbidopa and foslevodopa) as the first subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of motor fluctuations in adults with advanced PD. The approval was supported by results from a pivotal Phase 3 head-to-head, randomized and controlled clinical trial that demonstrated a statistically significant improvement in "on" time without troublesome dyskinesia and decreased "off" time, compared to oral immediate-release carbidopa/levodopa (CD/LD). AbbVie and Aliada Therapeutics announced a definitive agreement under which AbbVie will acquire Aliada, a biotechnology company advancing therapies using a novel blood-brain barrier (BBB)-crossing technology to address challenging central nervous system (CNS) diseases. Aliada's lead investigational asset utilizing this delivery technology, ALIA-1758, is an anti-pyroglutamate amyloid beta (3pE-Aβ) antibody in development for the treatment of Alzheimer's disease (AD). The acquisition also allows AbbVie to utilize Aliada's novel BBB-crossing technology to enhance discovery and development efforts across neuroscience. AbbVie and Gedeon Richter announced a new discovery, co-development and license agreement to advance novel targets for the potential treatment of neuropsychiatric conditions. This collaboration expands upon the success of nearly two decades of partnership on CNS projects. AbbVie announced the European Commission (EC) approved Skyrizi (risankizumab) for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to conventional or biologic therapy. The approval was supported by data from two pivotal Phase 3 trials in which Skyrizi achieved the primary endpoint of clinical remission as well as key secondary endpoints. This marketing authorization for Skyrizi marks its fourth approved indication in the European Union (EU). Skyrizi is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally. At the European Academy of Dermatology and Venerology (EADV) Congress 2024, AbbVie shared more than 30 presentations that showcased the depth and strength of AbbVie's dermatology portfolio. Presentations highlighted data for Rinvoq (upadacitinib), Skyrizi and lutikizumab across a multitude of dermatological conditions. AbbVie announced that the EC granted conditional marketing authorization for Tepkinly (epcoritamab) as a monotherapy for the treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of prior therapy. Tepkinly is the first subcutaneous bispecific antibody conditionally approved as a monotherapy in the EU to treat both r/r FL and r/r diffuse large B-cell lymphoma (DLBCL), after two or more lines of prior therapy. The EC approval is supported by data from the Phase 1/2 EPCORE NHL-1 clinical trial, which evaluated the safety and efficacy of Tepkinly in adult patients with r/r FL. Tepkinly is being co-developed by AbbVie and Genmab. AbbVie announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the marketing authorization of Elahere (mirvetuximab soravtansine) for the treatment of adult patients with folate receptor alpha (FRα)-positive, platinum-resistant and high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who have received one to three prior treatment regimens. The CHMP's opinion is supported by results of the Phase 3 MIRASOL clinical trial and the EC decision on this indication for Elahere is anticipated later this year. AbbVie announced submission of a Biologics License Application (BLA) to the FDA for accelerated approval (AA) of Teliso-V (telisotuzumab vedotin) in adult patients with previously treated, locally advanced or metastatic epidermal growth factor receptor (EGFR) wild type, nonsquamous non-small cell lung cancer (NSCLC) with c-Met protein overexpression. The BLA is supported by data from the Phase 2 LUMINOSITY clinical trial and review of the BLA will be conducted under FDA's Oncology Center of Excellence (OCE) Real-Time Oncology Review (RTOR) program. There are currently no approved anti-cancer therapies specifically for c-Met overexpressing NSCLC and if approved, Teliso-V would be the first-in-class therapy for this patient population. At the European Society for Medical Oncology (ESMO) Congress 2024, AbbVie showcased new data from its innovative antibody-drug conjugate (ADC) platform in tumor types with high unmet needs. Highlights included full data from the primary analysis of the positive, single-arm Phase 2 PICCOLO trial, evaluating Elahere for high FRα expressing platinum-sensitive ovarian cancer (PSOC); patient reported outcomes from the Phase 2 LUMINOSITY trial, evaluating Teliso-V in advanced NSCLC; as well as new safety and efficacy data in pre-treated patients with advanced NSCLC and gastroesophageal (GEA) cancer, from a Phase 1 study of ABBV-400 (telisotuzumab adizutecan). Allergan Aesthetics announced the FDA approved Botox Cosmetic (onabotulinumtoxinA) for temporary improvement in the appearance of moderate to severe vertical bands connecting the jaw and neck (platysma bands) in adults. Botox Cosmetic is the first product with four aesthetic indication areas: forehead lines, frown lines, crow's feet lines, and now platysma bands, making it the first product of its kind to go beyond the face. Allergan Aesthetics announced the launch of Botox Cosmetic for the treatment of masseter muscle prominence (MMP) in China. The approval is supported by Botox Cosmetic's well-established safety profile as well as clinical trial data that demonstrated Botox Cosmetic is effective in reducing the prominence of the masseter muscle. Botox Cosmetic is the first neurotoxin approved in China for MMP, the largest global MMP market. Allergan Aesthetics intends to develop Botox Cosmetic treatment for MMP in additional global markets and expand the use of Botox Cosmetic in the lower face. At the American Society for Dermal Surgery (ASDS), Allergan Aesthetics presented a total of 12 abstracts that showcased its commitment to patient outcomes and detailed insights and understanding of key concerns across differentiated patient segments. Highlights included four Best of Cosmetic Abstracts as well as a panel discussion on the impact of social media on patient experience and expectations when considering aesthetic treatment. Full-Year 2024 Outlook AbbVie is raising its adjusted diluted EPS guidance for the full year 2024 from $10.67 - $10.87 to $10.90 - $10.94, which includes an unfavorable impact of $0.64 per share related to acquired IPR&D and milestones expense incurred year-to-date through the third quarter 2024. The company's 2024 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred beyond the third quarter of 2024, as both cannot be reliably forecasted. Any potential IPR&D and milestones expense related to the recently announced acquisition of Aliada Therapeutics is also excluded from AbbVie's 2024 adjusted diluted EPS guidance, as the transaction is expected to close in the fourth quarter of 2024. Company Declares Dividend Increase of 5.8 Percent AbbVie is announcing today that its board of directors declared an increase in the company's quarterly cash dividend from $1.55 per share to $1.64 per share beginning with the dividend payable on February 14, 2025 to shareholders of record as of January 15, 2025. This reflects an increase of approximately 5.8 percent, continuing AbbVie's strong commitment to returning cash to shareholders through a growing dividend. Since the company's inception in 2013, AbbVie has increased its quarterly dividend by 310 percent. AbbVie is a member of the S&P Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years. 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 and eye care - and products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @abbvie on X (formerly Twitter), Facebook, Instagram, YouTube or LinkedIn. Conference Call AbbVie will host an investor conference call today at 8:00 a.m. Central Time to discuss our third-quarter performance. The call will be webcast through AbbVie's Investor Relations website at investors.abbvie.com. An archived edition of the call will be available after 11:00 a.m. Central Time. Non-GAAP Financial Results Financial results for 2024 and 2023 are presented on both a reported and a non-GAAP basis. Reported results were prepared in accordance with GAAP and include all revenue and expenses recognized during the period. Non-GAAP results adjust for certain non-cash items and for factors that are unusual or unpredictable, and exclude those costs, expenses, and other specified items presented in the reconciliation tables later in this release. AbbVie's management believes non-GAAP financial measures provide useful information to investors regarding AbbVie's results of operations and assist management, analysts, and investors in evaluating the performance of the business. Non-GAAP financial measures should be considered in addition to, and not as a substitute for, measures of financial performance prepared in accordance with GAAP. 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 and uses of future or conditional verbs, 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 expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 2023 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its Quarterly Reports on Form 10-Q and in other documents that AbbVie subsequently files with the Securities and Exchange Commission that update, supplement or supersede such information. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. SOURCE AbbVie WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultDrug ApprovalPhase 3License out/inAcquisition

29 Oct 2024

·www.prnewswire.com

Curis Announces $12.1 Million Registered Direct and Concurrent Private Placement

LEXINGTON, Mass., Oct. 29, 2024 /PRNewswire/ -- Curis, Inc. ("Curis") (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib (CA-4948), an orally available, small molecule IRAK4 inhibitor, today announced that it has entered into a definitive agreement with a combination of existing and new investors for the purchase of 2,398,414 shares of its common stock in a registered direct offering priced at-the-market under Nasdaq rules. In a concurrent private placement, Curis also agreed to issue to the investors in the registered direct offering unregistered warrants to purchase up to an aggregate of 2,398,414 shares of common stock. The unregistered warrants to be issued in the concurrent private placement will have an exercise price of $4.92 per share of common stock, will be exercisable immediately and will expire five years following the issuance date. The combined purchase price for one share of common stock and the associated unregistered warrant is $5.045. Gross proceeds to Curis from the offering are expected to be approximately $12.1 million, before deducting the placement agents' fees and other offering expenses payable by Curis. Curis intends to use the net proceeds from the offering on research, development, working capital, and other general corporate purposes. The registered direct offering and concurrent private placement are each expected to close on or about October 30, 2024, subject to the satisfaction of customary closing conditions. Truist Securities and Laidlaw & Company (U.K.) Ltd. are acting as placement agents for the registered direct offering and the concurrent private placement. The shares of common stock offered in the registered direct offering (but excluding the unregistered warrants to be issued in the concurrent private placement and shares of common stock underlying the unregistered warrants) are being offered by Curis pursuant to a shelf registration statement on Form S-3 (File No. 333-276950) that was filed with the U.S. Securities and Exchange Commission ("SEC") on February 8, 2024 and declared effective by the SEC on April 12, 2024. A prospectus supplement relating to and describing the terms of the registered direct offering will be filed with the SEC and will be available on the SEC's website at . The registered direct offering is being made only by means of a prospectus and related prospectus supplement. When available, electronic copies of the prospectus supplement and the accompanying prospectus may also be obtained from Truist Securities, Inc., Attention: Prospectus Department, 3333 Peachtree Road NE, 9th floor, Atlanta, Georgia 30326, by telephone at (800) 685-4786, or by email at [email protected]; and Laidlaw & Company (U.K.) Ltd., Attention: [email protected]. The unregistered warrants are being offered in the concurrent private placement pursuant to an exemption from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"), provided in Section 4(a)(2) of the Securities Act and/or Regulation D promulgated thereunder and, along with the shares of common stock underlying such unregistered warrants, have not been registered under the Securities Act or applicable state securities laws. Curis has agreed to file a resale registration statement with the SEC covering the resale of the shares of common stock underlying the unregistered warrants. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. About Curis, Inc. Curis is a biotechnology company focused on the development of emavusertib, an orally available, small molecule IRAK4 inhibitor. Emavusertib is currently undergoing testing in the Phase 1/2 TakeAim Lymphoma study (CA-4948-101) in patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) in combination with the BTK inhibitor ibrutinib, as a monotherapy in the Phase 1/2 TakeAim Leukemia study (CA-4948-102) in patients with relapsed/refractory acute myeloid leukemia (AML) and relapsed/refractory high risk myelodysplastic syndrome (hrMDS) with either a FLT3 mutation or a splicing factor mutation (U2AF1 or SF3B2), and as a frontline combination therapy with azacitidine and venetoclax in patents with AML (CA-4948-104). Emavusertib has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML and MDS and from the European Commission for the treatment of PCNSL. Curis, through its 2015 collaboration with Aurigene, has the exclusive license to emavusertib (CA-4948). Curis licensed its rights to Erivedge® to Genentech, a member of the Roche Group, under which they are commercializing Erivedge® for the treatment of advanced basal cell carcinoma. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including, without limitation, any statements with respect to Curis's registered direct offering and concurrent private placement, anticipated use of proceeds, prospects for Curis and the expected closing of the registered direct offering and the concurrent private placement. Forward-looking statements may contain the words "believes," "expects," "anticipates," "plans," "intends," "seeks," "estimates," "assumes," "predicts," "projects," "targets," "will," "may," "would," "could," "should," "continue," "potential," "focus," "strategy," "mission" or similar expressions. Actual results may differ materially from those indicated by such forward-looking statements. Factors that may cause such a difference include, without limitation, risks and uncertainties related to market and other conditions, the satisfaction of customary closing conditions related to the registered direct offering and the concurrent private placement and the impact of general economic, industry or political conditions in the United States or internationally. There can be no assurance that Curis will be able to complete the registered direct offering and the concurrent private placement on the anticipated terms, or at all. You should not place undue reliance on these forward-looking statements. Additional risks and uncertainties relating to the registered direct offering, Curis and its business can be found under the caption "Risk Factors" included in Curis's Annual Report on Form 10-K for the year ended December 31, 2023, Curis's prospectus supplement to be filed with the SEC, and in other filings that Curis periodically makes with the SEC. In addition, any forward-looking statements included in this press release represent the view of Curis only as of today and should not be relied upon as representing Curis's views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise, except as may be required by law. SOURCE Curis, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Orphan DrugLicense out/inClinical Study

25 Oct 2024

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Oncternal Therapeutics Announces Updated Safety and Efficacy Data for Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer

Oct. 22, 2024 -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT) (the “Company”) today announced updated data from its Phase 1/2 Study of ONCT-534 for the treatment of patients with relapsed or refractory metastatic Castration-Resistant Prostate Cancer (mCRPC). Based on initial pharmacokinetic results, two additional dosing cohorts with twice daily (BID) oral dosing of ONCT-534 had been incorporated in the Phase 1/2 study ONCT-534-101 (NCT05917470). Overall, fifteen patients received ONCT-534 once daily (QD) in six dosing cohorts and six patients received ONCT-534 BID in two dosing cohorts. Based on a data cut off of September 30, 2024, the BID dosing schedule was well tolerated, with no related Grade 3 or higher toxicities. One patient, who experienced a rising PSA on ONCT-534 at 160 mg BID, had a subsequent 50% reduction in PSA after four weeks of ONCT-534 at 300 mg BID, and at the same time the CAT Scan showed a 16% reduction in target lesions compared to baseline. Enumeration and biomarker analysis of circulating tumor cells (CTCs) showed promising effects on expression of androgen receptor (AR)-regulated genes, and AR nuclear translocation in six additional patients. CTC analysis also showed that some patients who did not respond to ONCT-534 had prostate cancer that had developed neuroendocrine features, which are associated with AR independent disease. “While we still believe the decision to discontinue the ONCT-534-101 clinical trial remains the correct one in the current biotechnology environment, the updated clinical results highlight the potential of ONCT-534 in prostate cancer. We believe there is value in exploring BID dosing further, as well as studying ONCT-534 in earlier lines of therapy for advanced prostate cancer,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “We continue to explore strategic alternatives for our product candidates, including ONCT-534, ONCT-808, zilovertamab and ONCT-216 in an ongoing effort to maximize value to our shareholders.” Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. More information on our company and programs is available at https://oncternal.com/. ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR mutation and aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. It was investigated in Study ONCT-534-101 (NCT05917470) for the treatment of patients with mCRPC who are resistant to current AR pathway inhibitors. ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced compared with currently approved CAR T products. It was investigated in Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. Zilovertamab (previously called cirmtuzumab and UC-961) is an investigational monoclonal antibody designed to inhibit the function of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1). Zilovertamab has been evaluated in Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in 100% progression free survival (PFS) at 48 months in CLL patients whose tumors harbored del(17p)/p53 mutation, a population underserved by current treatment options. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to zilovertamab for the treatment of CLL and MCL. The results of an investigator-sponsored, Phase 1b clinical trial of zilovertamab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer were recently published (Shatsky 2023). Zilovertamab was evaluated in an investigator-initiated Phase 1b study of zilovertamab in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905), and an investigator-initiated Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory (R/R) CLL (NCT04501939). ONCT-216 (previously called TK216) is an investigational targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as acute myeloid leukemia (AML), diffuse large B cell lymphoma (DLBCL), and prostate cancer. In preclinical models, ONCT-216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation, Orphan Drug Designation and Fast Track Status to ONCT-216 for the treatment of Ewing sarcoma. The results of a Phase 1/ 2 clinical trial of ONCT-216 in patients with Ewing sarcoma (NCT02657005) were recently published (Myers 2024). The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultOrphan DrugFast TrackImmunotherapy

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KEGG	Wiki	ATC	Drug Bank
D10223	Ibrutinib	L01XE27	DB09053

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Lymphoplasmacytic Lymphoma	JP	Janssen Pharmaceutical KK	23 Dec 2022
Graft vs Host Disease	JP	Janssen Pharmaceutical KK	27 Sep 2021
Marginal Zone B-Cell Lymphoma	US	Pharmacyclics LLC	18 Jan 2017
Chronic graft-versus-host disease	MX	Janssen-Cilag SA de CV	01 Mar 2015
Small Lymphocytic Lymphoma	MX	Janssen-Cilag SA de CV	01 Mar 2015
Mantle cell lymphoma recurrent	EU	Janssen-Cilag International NV	21 Oct 2014
Mantle cell lymphoma recurrent	NO	Janssen-Cilag International NV	21 Oct 2014
Mantle cell lymphoma recurrent	LI	Janssen-Cilag International NV	21 Oct 2014
Mantle cell lymphoma recurrent	IS	Janssen-Cilag International NV	21 Oct 2014
Mantle cell lymphoma refractory	NO	Janssen-Cilag International NV	21 Oct 2014
Mantle cell lymphoma refractory	LI	Janssen-Cilag International NV	21 Oct 2014
Mantle cell lymphoma refractory	IS	Janssen-Cilag International NV	21 Oct 2014
Mantle cell lymphoma refractory	EU	Janssen-Cilag International NV	21 Oct 2014
Waldenstrom Macroglobulinemia	KR	Janssen Korea Ltd.	08 Aug 2014
Chronic Lymphocytic Leukemia	US	Pharmacyclics LLC	12 Feb 2014
Mantle-Cell Lymphoma	US	Pharmacyclics LLC	13 Nov 2013

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Small Lymphocytic Lymphoma	Phase 3	IT	Pharmacyclics LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	PL	Pharmacyclics LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	BE	Janssen Research & Development LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	US	Janssen Research & Development LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	ES	Pharmacyclics LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	PL	Janssen Research & Development LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	GB	Janssen Research & Development LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	FR	Janssen Research & Development LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	BE	Pharmacyclics LLC	01 Jun 2012
Small Lymphocytic Lymphoma	Phase 3	ES	Janssen Research & Development LLC	01 Jun 2012

Clinical Result

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Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02927964 (CTgov)	Phase 1/2	Recurrent Follicular Lymphoma \| Mantle-Cell Lymphoma \| Refractory Grade 3a Follicular Lymphoma \| Refractory Follicular Lymphoma \| Marginal Zone B-Cell Lymphoma	21	TLR9 Agonist SD-101+Ibrutinib (Phase 1b -SD-101 3mg: Treatment (Radiation Therapy, TLR9 Agonist SD-101, Ibrutinib))	kymfcgpurf(kjpdunsrrf) = gjtefojlwt qzmqhybmvr (nsckkypaqg, jraortecfg - gltotuauar) View more	-	16 Oct 2024
				TLR9 Agonist SD-101+Ibrutinib (Phase II -SD-101 3mg: Treatment (Radiation Therapy, TLR9 Agonist SD-101, Ibrutinib))	kymfcgpurf(kjpdunsrrf) = ymsdabeemn qzmqhybmvr (nsckkypaqg, pcjblhvgds - tcjwaxvzgd) View more
NCT02692248 (phase II, CTgov)	Phase 2	Diffuse Large B-Cell Lymphoma \| Diffuse large B-cell lymphoma recurrent	64	Ibrutinib+Gemcitabine+Oxaliplatin+Dexamethasone+Rituximab	hahxvksbdq(hqlpemjbcb) = oumyqsgbxt hsygicwqys (muvotmjhux, dtywieycje - rsyjasdcei) View more	-	10 Oct 2024
NCT03136497 (CTgov)	Phase 1	Diffuse large B-cell lymphoma refractory \| Diffuse large B-cell lymphoma recurrent	10	Ibrutinib+400mg ABT-199+Rituximab (400mg ABT-199)	mealhmpvhc(helcigojcp) = jihmkudnlf qoytoxlpbs (cgpwftdnjr, vnntxahntg - yrfgjojyuv) View more	-	23 Sep 2024
				Ibrutinib+800mg ABT-199+Rituximab (800mg ABT-199)	mealhmpvhc(helcigojcp) = kunwkexbas qoytoxlpbs (cgpwftdnjr, pvssmzhwas - atlghnbese) View more
NCT04446962 (LOC-R01, Pubmed \| J Hematol Oncol)	Phase 1/2	Primary Central Nervous System Lymphoma First line	-	Ibrutinib	(hloblzglft) = fkklvyeeih ytbpanvkoe (egnccnfkdc ) View more	Positive	19 Sep 2024
				Lenalidomide	(hloblzglft) = eqkpazengy ytbpanvkoe (egnccnfkdc ) View more
NCT01724346 (CTgov)	Phase 3	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma	269	Next-line ibrutinib (Ibrutinib)	dfmqaoiebp(dctszqiuvr) = ydyugumaso rkjcoinqfc (njamrdeark, lvtczzfoze - krtjqykhkn) View more	-	19 Sep 2024
				Ibrutinib (Chlorambucil)	dfmqaoiebp(dctszqiuvr) = bsoitabamr rkjcoinqfc (njamrdeark, rksoruojok - yohjtpkqmt) View more
NCT02315326 (Pubmed) Manual	Phase 2	Secondary Central Nervous System Lymphoma \| Primary Central Nervous System Lymphoma circulating tumor DNA	46	Ibrutinib (PCNSL)	(jekvaidwcb) = xancsodjse mureoguivk (cwlxnjcmsn, 2.8 - 9.2) View more	Positive	12 Jul 2024
				Ibrutinib (SCNSL)	(jekvaidwcb) = bjuypeubdb mureoguivk (cwlxnjcmsn, 1.3 - 14.5) View more
NCT03939182 (NEWS) Manual	Phase 1	Mantle-Cell Lymphoma	-	艾贝司他，伊布替尼	(ptrsgablbb) = 艾贝司他联合伊布替尼有效率（CR和ORR）及无进展生存期（PFS）均优于单独使用伊布替尼 mnrsafwqil (dczqtyyuic )	Positive	28 Jun 2024
				伊布替尼
NCT03734016 (ALPINE, Pubmed) Manual	Phase 3	Chronic Lymphocytic Leukemia \|	90	Zanubrutinib 160 mg twice-daily	(tjurvqgocn) = nlwcfxcvrz tmsvbdzart (enrtseempb ) View more	Positive	18 Jun 2024
				Ibrutinib 420 mg once-daily	(tjurvqgocn) = mohtbbxvke tmsvbdzart (enrtseempb ) View more
NCT03332173 \| NCT04170283 \| NCT03846427 \| NCT03189524 \| NCT03053440 \| NCT02343120 \| NCT03206918 \| NCT03734016 \| NCT03206970 \| NCT03336333 (Pubmed \| Blood Adv)	Not Applicable	Chronic Lymphocytic Leukemia	1,550	Zanubrutinib	(sjrlqycdaj) = gauewafijg uyjlpimbrr (srjhxmfonj )	Positive	28 May 2024
				Ibrutinib	(sjrlqycdaj) = xoaefyyxia uyjlpimbrr (srjhxmfonj )
ASCEND (ASCO2024) Manual	Not Applicable	Chronic Lymphocytic Leukemia	-	Zanubrutinib (High-Risk With COVID-19 Adjustment)	(qsrjqalzwe): 0.54 (95% CI, 0.32 - 0.92) View more	Positive	24 May 2024
				Acalabrutinib (High-Risk With COVID-19 Adjustment)

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