To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis

Start Date26 Nov 2024

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

NCT05949099

/ RecruitingPhase 2IIT

Phase II Study of Cryoablation and Nirogacestat for Desmoid Tumor

The primary purpose of this protocol is Systemic therapy with oral study agent, nirogacestat, followed by a single cryoablation procedure.

Start Date15 Aug 2023

Sponsor / Collaborator

Stanford University

[+1]

NCT05573802

/ RecruitingPhase 1/2IIT

A Phase 1/2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administrated in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma

This is a phase 1/2, open-label study designed to assess the safety and clinical activity of different belantamab mafodotin doses in combination with lenalidomide, dexamethasone and nirogacestat in patients with transplant ineligible newly diagnosed multiple myeloma.
This will be a 2-part study. In part 1 participants will be enrolled in one cohort to receive belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat and will determine the recommended phase 2 dose (RP2D) to be further evaluated for safety and clinical activity in the dose expansion cohort. The RP2D dose will be used in future studies in the transplant-ineligible newly diagnosed multiple myeloma (NDMM) setting. In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 of the study will also evaluate an alternative dose modification guideline for corneal adverse events (AEs).
Overall, approximately 36 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is enrolled (follow-up period range: 3-4 years). The estimated accrual period will be 12 months, corresponding to an approximate total study duration of 4 years.

Start Date14 Jul 2023

Sponsor / Collaborator

Hellenic Society of Cardiology

[+1]

100 Clinical Results associated with Nirogacestat hydrobromide

100 Translational Medicine associated with Nirogacestat hydrobromide

100 Patents (Medical) associated with Nirogacestat hydrobromide

Literatures (Medical) associated with Nirogacestat hydrobromide

01 Dec 2024·Biochemical Pharmacology

Activation of the γ-secretase/NICD-PXR/Notch pathway induces Taxol resistance in triple-negative breast cancer

Article

Author: Jia, Hui ; Wang, Zuo-Jun ; Ma, Liang-Yu ; Zhan, Xiang-Yi ; Yao, Kuo ; Zhou, Ming-Sheng ; Kumar Santhanam, Ramesh ; Dai, Han-Yu

Triple-negative breast cancer (TNBC) is currently the only subtype lacking efficient targeted therapies. Taxol is the primary chemotherapeutic agent for TNBC. However, Taxol resistance often develops in the treatment of TNBC patients, which importantly contributes to high mortality and poor prognosis in TNBC patients. Recent preclinical studies have shown that the inhibition of Notch pathway by γ-secretase inhibitors can slow down the progression of TNBC. Our studies in bioinformatic analysis of breast cancer patients and TNBC/Taxol cells in vitro showed that there was high correlation between the activation of Notch pathway and Taxol resistance in TNBC. Increased γ-secretase activity (by the overexpression of catalytic core PSEN-1) significantly reduced Taxol sensitivity of TNBC cells, and enhanced biological characteristics of malignancy in vitro, and tumour growth in vivo. Mechanistically, increased γ-secretase activity led to the accumulation of NICD in the nucleus, promoting the interaction between NICD and PXR to activate PXR, which triggered the transcription of PXR downstream associated drug resistance genes. Furthermore, we showed that pharmacological inhibition of γ-secretase with γ-secretase inhibitors (Nirogacestat and DAPT) can reverse Taxol resistance in vivo and in vitro. Our results for the first time demonstrate that the activation of γ -secretase/NCD-PXR/Notch pathway is one of important mechanisms to cause Taxol resistance in TNBC, and the blockades of this pathway may represent a new therapeutic strategy for overcoming Taxol resistance in TNBC.

01 Nov 2024·Expert Opinion on Pharmacotherapy

Examining nirogacestat for adults with progressing desmoid tumors who require systemic treatment

Review

Author: Campos, Fernando ; Kasper, Bernd

INTRODUCTIONDesmoid tumor (DT) is a rare, locally aggressive, mesenchymal neoplasm that can arise at any site in the body. Medical therapies play a major role for DT's patients requiring treatment. A novel systemic approach has recently emerged with Nirogacestat, a γ-secretase inhibitor targeting the NOTCH signaling pathway.AREAS COVEREDNirogacestat is the first drug in its class to receive approval from the Food and Drug Administration (FDA) and is the first FDA-approved treatment specifically for DTs. We reviewed the data leading to its discovery, including its mechanism of action, pharmacological properties, clinical efficacy, and its positioning within the current treatment armamentarium for DTs.EXPERT OPINIONHigh-quality evidence for systemic therapies in the management of DTs remains an unmet need. Nirogacestat now joins sorafenib as the only drugs with efficacy in DTs demonstrated by randomized phase 3 studies. Currently, there are no comparative trials of the available systemic therapies. Therefore, physicians should consider factors such as drug accessibility, cost, toxicity profile, comorbidities, and patient preferences when selecting treatment. Long-term efficacy and safety data will be essential for evaluating the duration of treatment response and monitoring late-onset side effects of Nirogacestat.

07 Oct 2024·Journal of Cell Biology

Calorie restriction activates a gastric Notch-FOXO1 pathway to expand ghrelin cells

Article

Author: Mukhanova, Maria ; Accili, Domenico ; Deng, Zhaobin ; Kitamoto, Takumi ; Spiegel, Sophia ; Pajvani, Utpal ; Du, Wen ; Kraakman, Michael ; McKimpson, Wendy M. ; Yu, Junjie

Calorie restriction increases lifespan. Among the tissue-specific protective effects of calorie restriction, the impact on the gastrointestinal tract remains unclear. We report increased numbers of chromogranin A-positive (+), including orexigenic ghrelin+ cells, in the stomach of calorie-restricted mice. This effect was accompanied by increased Notch target Hes1 and Notch ligand Jag1 and was reversed by blocking Notch with DAPT, a gamma-secretase inhibitor. Primary cultures and genetically modified reporter mice show that increased endocrine cell abundance is due to altered Lgr5+ stem and Neurog3+ endocrine progenitor cell proliferation. Different from the intestine, calorie restriction decreased gastric Lgr5+ stem cells, while increasing a FOXO1/Neurog3+ subpopulation of endocrine progenitors in a Notch-dependent manner. Further, activation of FOXO1 was sufficient to promote endocrine cell differentiation independent of Notch. The Notch inhibitor PF-03084014 or ghrelin receptor antagonist GHRP-6 reversed the phenotypic effects of calorie restriction in mice. Tirzepatide additionally expanded ghrelin+ cells in mice. In summary, calorie restriction promotes Notch-dependent, FOXO1-regulated gastric endocrine cell differentiation.

111

News (Medical) associated with Nirogacestat hydrobromide

13 Jan 2025

·www.globenewswire.com

SpringWorks Therapeutics Reports Preliminary Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates at 43rd Annual J.P. Morgan Healthcare Conference

– Achieved $61.5 million and $172.0 million in preliminary fourth quarter and full year 2024 OGSIVEO® (nirogacestat) U.S. net product revenues, respectively – – Ended 2024 with approximately $462 million in cash, cash equivalents, and marketable securities – – Additional updates across Company’s commercial portfolio and investigational pipeline to be provided during J.P. Morgan Healthcare conference presentation today at 11:15 a.m. PT – STAMFORD, Conn., Jan. 13, 2025 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, today announced its preliminary fourth quarter and full year 2024 U.S. net product revenue for OGSIVEO® (nirogacestat) and provided additional company updates ahead of its presentation at the 43rd Annual J.P. Morgan Healthcare conference. Preliminary Fourth Quarter and Full Year 2024 Financial Results* and Recent Business Highlights Preliminary fourth quarter and full-year 2024 U.S. net product revenue for OGSIVEO were $61.5 million and $172.0 million, respectively.As of December 31, 2024, total preliminary cash, cash equivalents, and marketable securities was $461.9 million. SpringWorks expects its cash position to fund operations through profitability, which the Company anticipates achieving in the first half of 2026.Presented long-term follow-up data from the Phase 3 DeFi trial of nirogacestat in adults with progressing desmoid tumors in the fourth quarter of 2024. These results showed that longer-term treatment with nirogacestat (median duration of treatment: 34 months) was associated with further reductions in tumor size, increase in objective response rate with additional partial responses and complete responses, sustained improvements in desmoid tumor symptoms including pain, and a consistent safety profile.Obtained an exclusive, global license from Rappta Therapeutics Oy for a first-in-class molecular glue of specific Protein Phosphatase 2A (PP2A) complexes. PP2A mutations represent a class of targetable oncogenic drivers in molecularly defined subsets of uterine cancer patients with high unmet need. In preclinical models of PP2A mutant uterine cancer, SW-3431 (formerly RPT04402) showed rapid, deep and durable tumor regressions as a monotherapy. In exchange for the license, Rappta received a $13 million upfront payment and is eligible to receive further clinical, regulatory and commercial milestone payments, and tiered single digit royalties on net sales. * The preliminary fourth quarter and full year 2024 financial results are unaudited and do not present all information necessary for an understanding of the Company’s results of operations and financial position for the fourth quarter and full year 2024. Such financial results are subject to adjustment and could differ from the Company’s announcement of complete financial results in February 2025. 2025 Priorities and Anticipated Milestones OGSIVEO (nirogacestat) Continue strong commercial execution of the OGSIVEO launch in the U.S.Secure regulatory approval for OGSIVEO in the European Union (EU) and launch OGSIVEO following reimbursement authorization in individual EU countries, beginning with Germany in mid-2025.Publish long-term follow-up data from the Phase 3 DeFi trial of nirogacestat in adults with desmoid tumors in a peer-reviewed journal by the end of 2025.Report initial data from the Phase 2 trial evaluating nirogacestat as a monotherapy in patients with ovarian granulosa cell tumors in the first half of 2025.Continue to support several industry and academic collaborator studies evaluating nirogacestat as part of B-cell maturation antigen (BCMA) combination therapy regimens across treatment lines in patients with multiple myeloma. Mirdametinib (NF1-PN) Secure FDA approval in adults and children with NF1-associated plexiform neurofibromas, or NF1-PN (PDUFA: February 28, 2025), and launch in the U.S.Obtain regulatory approval in the EU for mirdametinib for the treatment of adults and children with NF1-PN and begin initial launch in 2025. Emerging Pipeline SpringWorks expects additional data to be presented by MapKure from the brimarafenib monotherapy trial in the second half of 2025.Continue enrolling patients in Phase 1 trial of SW-682 in Hippo-mutant solid tumors.File an Investigational New Drug (IND) application for SW-3431 by the end of 2025. “2025 is set up to be another transformative year for SpringWorks. With the potential launch of our second medicine and global expansion to serve patients with two devastating diseases, we are energized by the opportunity to continue delivering on the commitments we have made to the patient communities we are dedicated to serving,” said Saqib Islam, Chief Executive Officer of SpringWorks. “In parallel with our commercial launches, we are advancing our pipeline of oncology programs for heavily underserved patient populations and are confident that our strong foundation will drive our long-term growth and success.” Presentation at the 43rd Annual J.P. Morgan Healthcare Conference SpringWorks will webcast its presentation from the 43rd Annual J.P. Morgan Healthcare Conference today, Monday, January 13, 2025 at 11:15 a.m. PT (2:15 p.m. ET). To access the live webcast, please visit the Events & Presentations page within the Investors & Media section of the company’s website at https://ir.springworkstx.com. A replay of the webcast will be available on SpringWorks’ website for a limited time following the conference. About SpringWorks Therapeutics SpringWorks is a commercial-stage biopharmaceutical company applying a precision medicine approach to developing and delivering life-changing medicines for people with severe rare diseases and cancer. OGSIVEO® (nirogacestat), approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, is the Company’s first FDA-approved therapy. SpringWorks also has a diversified targeted therapy pipeline spanning solid tumors and hematological cancers, with programs ranging from preclinical development through advanced clinical trials. In addition to its wholly owned programs, SpringWorks has also entered into multiple collaborations with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients in need. For more information, visit www.springworkstx.com and follow @SpringWorksTx on X (formerly Twitter), LinkedIn, and YouTube. SpringWorks uses its website as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD. Such disclosures will be included on SpringWorks' website in the Investors & Media section. Accordingly, investors should monitor such portions of the SpringWorks website, in addition to following press releases, SEC filings and public conference calls and webcasts. SpringWorks Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, relating to our business, operations, and financial conditions, including but not limited to our preliminary financial results for the fourth quarter and full year 2024, current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development and commercialization plans, the timing of and results from our preclinical studies and clinical trials, the potential for mirdametinib to become an important new treatment for adult and pediatric NF1-PN patients, expectations regarding the timing and results of the reviews by the FDA and the EMA, as applicable, of each of the NDA and the MAA for mirdametinib for the treatment of adult and pediatric NF1-PN patients, including the FDA's PDUFA target action date for the NDA, expectations regarding the timing and results of the MAA for OGSIVEO and our plans to make OGSIVEO commercially available in individual countries in the European Union following required approvals beginning in mid-2025, our plans to present additional data from the Phase 3 DeFi trial of nirogacestat at upcoming conferences, our plans for seeking regulatory approval for and making mirdametinib available for NF1-PN patients, if approved, expectations regarding the timing and initial data from the Phase 2 trial evaluating nirogacestat in patients with recurrent ovarian granulosa cell tumors, our expectations and timing for additional data for brimarafenib in the second half of 2025, our expectations and the timing of the Phase 1 trial of SW-682, our plans to file an IND for SW-3431 by the end of 2025, as well as relating to other future conditions. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “would,” “should” and “could,” and similar expressions or words, identify forward-looking statements. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks relating to: (i) the success of our commercialization efforts with respect to OGSIVEO, (ii) our limited experience as a commercial company, (iii) our ability to obtain or maintain adequate coverage and reimbursement for OGSIVEO, (iv) the success and timing of our product development activities, including the initiation and completion of our clinical trials, (v) our expectations regarding the potential clinical benefit of OGSIVEO for adult patients with desmoid tumors who require systemic treatment, (vi) estimates regarding the number of adult patients who are diagnosed with desmoid tumors annually per year in the U.S. and the potential market for OGSIVEO, (vii) the fact that topline or interim data from clinical studies may not be predictive of the final or more detailed results of such study or the results of other ongoing or future studies, (viii) the success and timing of our collaboration partners’ ongoing and planned clinical trials, (ix) the timing of our planned regulatory submissions and interactions, including the timing and outcome of decisions made by the FDA, EMA, and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, (x) whether FDA, EMA, or other regulatory authorities will require additional information or further studies, or may fail or refuse to approve or may delay approval of our product candidates, including nirogacestat and mirdametinib, (xi) our ability to obtain regulatory approval of any of our product candidates or maintain regulatory approvals granted for our products, (xii) our plans to research, discover and develop additional product candidates, (xiii) our ability to enter into collaborations for the development of new product candidates and our ability to realize the benefits expected from such collaborations, (xiv) our ability to maintain adequate patent protection and successfully enforce patent claims against third parties, (xv) the adequacy of our cash position to fund our operations through any time period indicated herein, (xvi) our ability to establish manufacturing capabilities, and our and our collaboration partners’ abilities to manufacture our product candidates and scale production, and (xvii) our ability to meet any specific milestones set forth herein. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. For further information regarding the risks, uncertainties and other factors that may cause differences between SpringWorks’ expectations and actual results, you should review the “Risk Factors” in Item 1A of Part II of SpringWorks’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings. Contacts Investors investors@springworkstx.com Media media@springworkstx.com

Drug ApprovalPhase 1Phase 3License out/in

13 Jan 2025

·www.prnewswire.com

Rappta Therapeutics enters into a global license agreement with SpringWorks Therapeutics for a pre-clinical first-in-class molecular glue targeting PP2A

Goal to accelerate development and commercialization of the lead asset RPT04402 for the treatment of a subset of uterine cancers Financials include a $13 million upfront payment and potential for significant further milestones HELSINKI, Jan. 13, 2025 /PRNewswire/ -- Rappta Therapeutics ("Rappta"), focused on developing first-in-class anti-cancer drugs activating protein phosphatase 2A (PP2A), today announces an exclusive global license agreement with SpringWorks Therapeutics ("SpringWorks") for RPT04402, a first-in-class molecular glue of specific Protein Phosphatase 2A (PP2A) complexes. Rappta's PP2A-reactivating technologies developed using its proprietary high resolution structural data have the potential to create a new class of anti-cancer drugs for treating a broad range of human cancers. PP2A is a critical enzyme in regulating protein de-phosphorylation and its reactivation is fundamental for tumor suppression, but it has been historically hard to target. PP2A mutations are oncogenic drivers in molecularly defined subsets of uterine cancer and represent a targetable subset of patients with a high unmet clinical need. In pre-clinical models of PP2A mutant uterine cancer, RPT0402 achieved rapid, deep and durable tumor regressions at as monotherapy. Under the exclusive license agreement, SpringWorks Therapeutics will be responsible for global development and commercialization of RPT04402. SpringWorks has paid Rappta $13 million upfront, and Rappta is also eligible to receive further clinical, regulatory and commercial milestone payments, and tiered single-digit royalties on net sales. SpringWorks expects to file an Investigational New Drug (IND) application for RPT04402 by the end of 2025. Sunjeet Sawhney, Chief Executive Officer of Rappta Therapeutics, commented: "Rappta is the only company to have successfully targeted PP2A, a notoriously difficult and undruggable target. Data we generated demonstrated the potential of RPT04402 for treating large, underserved patient populations. SpringWorks, a leader in the targeted oncology space, has the expertise and knowledge to accelerate the further development of our first in class asset. I would like to thank our team and investors who have supported our journey and we look forward to following the progress made in this area" Goutham Narla, Chief Scientific Officer of Rappta Therapeutics and Professor of Internal Medicine and Human Genetics at the University of Michigan, said: "Our team at Rappta Therapeutics has been able to leverage our proprietary structural data to develop a first-in-class series of molecular glues to the previously undruggable tumor suppressor PP2A. We are excited to be able to work with SpringWorks to potentially translate this approach to the clinic with the hope that this approach will have broad applications for the treatment of human cancers." Rappta was founded by Goutham Narla & Mikko Mannerkoski, back in 2019 with funding from Novartis Venture Fund ("NVF"), Novo Holdings, Advent Life Sciences and a family office in Series A financing alongside other non-dilutive funding from Business Finland. About Rappta Therapeutics Rappta Therapeutics, a private biotech with operations in Finland and the US, is developing first-in-class anti-cancer drugs activating protein phosphatase 2A (PP2A). It has developed proprietary tools and a unique understanding of PP2A which allows it to therapeutically reactivate PP2A, a critical enzyme regulating protein de-phosphorylation and tumor growth, with the potential to create a new class of anti-cancer drugs. Rappta has a strong scientific, management and commercial team. Its scientific team, led by CSO and co-founder, Professor Goutham Narla, Former Division Chief of Genetic Medicine at the University of Michigan, represents world-leading expertise in PP2A. It is backed by blue-chip investors Advent Life Sciences, Novartis Venture Fund, Novo Seeds and a family office. For more information, go to . About PP2A Reversible phosphorylation is a fundamental mechanism controlling all cell signaling and communication and this process is regulated through the opposing actions of phosphatases (which remove phosphate groups from proteins) and kinases (which add phosphate groups to proteins). Altered cellular signaling because of protein hyperphosphorylation, results in the sustained growth of malignant cells and is a hallmark of human cancer development and progression. Protein Phosphatase 2A (PP2A) is a serine/threonine phosphatase that functions as a tumor suppressor by negatively regulating multiple oncogenic signaling pathways responsible for driving cancer progression. PP2A is made up of three subunits, that form a complete and active enzyme when bound together. The active enzyme is comprised of a scaffolding subunit (A), serving as the structural platform for the assembly of the catalytic (C) subunit and one substrate directing regulatory (B) subunit. In cancer, the tumor-suppressive activity of PP2A is often disrupted as a result of the inability of the three subunits to bind together correctly, rendering the PP2A enzyme inactive. This inactivation of PP2A, leads to increased oncogenic signaling, driving cancer progression and growth. Therefore, the reactivation of PP2A affords a unique therapeutic strategy to restore PP2A activity and cellular homeostasis, that can be used for the treatment of cancer and a broad range of other diseases. About SpringWorks Therapeutics SpringWorks is a commercial-stage biopharmaceutical company applying a precision medicine approach to developing and delivering life-changing medicines for people with severe rare diseases and cancer. OGSIVEO® (nirogacestat), approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, is the Company's first FDA-approved therapy. SpringWorks also has a diversified targeted therapy pipeline spanning solid tumors and hematological cancers, with programs ranging from preclinical development through advanced clinical trials. In addition to its wholly owned programs, SpringWorks has also entered into multiple collaborations with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients in need. For more information, visit and follow @SpringWorksTx on X (formerly Twitter), LinkedIn, and YouTube. SOURCE Rappta Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/inDrug Approval

11 Dec 2024

·www.businesswire.com

Iambic Therapeutics Announces Appointment of Peter Olson, Ph.D., as Chief Scientific Officer

SAN DIEGO--( BUSINESS WIRE )--Iambic Therapeutics, a clinical-stage biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, today announced the appointment of Peter Olson, Ph.D. to the role of chief scientific officer. Dr. Olson, who was most recently vice president, research at Mirati Therapeutics, a Bristol Myers Squibb (BMS) company, will join Iambic’s executive leadership team. A specialist in cancer biology and genetics, Dr. Olson will lead a team focused on driving small molecule programs from target identification through to clinical proof-of-concept. At Mirati, he led in vitro and in vivo pharmacology and translational research across its portfolio, which included pre-clinical efforts for KRAZATI™ (adagrasib), a KRAS G12C inhibitor approved by the US Food and Drug Administration (FDA) in 2022. “We couldn’t be more excited to welcome Pete Olson to the Iambic team,” said Tom Miller, PhD, Iambic’s chief executive officer. “He brings extraordinary drug discovery and development leadership experience as we advance and expand our pipeline of clinical candidates for oncology and other disease areas.” Iambic is developing an internal pipeline of candidates, discovered using its platform that integrates AI models for protein structure prediction and wholistic drug design with high-throughput chemistry and biology experimentation. The Company’s pipeline currently includes IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor for multiple cancer indications, an allosteric inhibitor for KIF18A, and additional new programs. “Iambic’s AI-driven discovery platform enables the rapid identification of promising drug molecules and provides predictive insights into clinical properties of potential medicines,” said Dr. Olson. “I am excited to join the Iambic team to further advance their promising pipeline as we work to deliver innovative breakthroughs for patients.” Dr. Olson has over twenty-five years of basic, pre-clinical and translational cancer biology experience in academia and industry and is the author of close to 50 peer-reviewed papers. Prior to Mirati he was a senior principal scientist in Pfizer’s Oncology Research Unit, where he was the translational project leader for OGSIVEO™, the first FDA approved treatment for progressive desmoid tumors. Before Pfizer, he was a postdoc in the Hanahan Laboratory at the University of California, San Francisco. He received his Ph.D. in Biology from the University of California, San Diego and a B.S. in Biochemistry from the University of California, Davis. About Iambic’s AI-Driven Discovery Platform The Iambic AI-driven platform was created to address the most challenging design problems in drug discovery, leveraging technology innovations such as Enchant, a multi-modal transformer model that predicts clinical outcomes from the earliest stages of discovery, and NeuralPLexer, the best-in-class predictor of protein and protein-ligand structures. The integration of physics principles into the platform’s AI architectures improves data efficiency and allows molecular models to venture widely across the space of possible chemical structures. The platform enables identification of novel chemical modalities for engaging difficult-to-address biological targets, discovery of defined product profiles that optimize therapeutic window, and multi-parameter optimization for highly differentiated development candidates. Through close integration of AI-generated molecular designs with automated experimental execution, Iambic completes design-make-test cycles on a weekly cadence. About Iambic Therapeutics Founded in 2019 and headquartered in San Diego, California, Iambic Therapeutics is disrupting the therapeutics landscape with its unique AI-driven drug-discovery platform. Iambic has assembled a world-class team that unites pioneering AI experts and experienced drug hunters with strong track records of success in delivering clinically validated therapeutics. The Iambic platform has been demonstrated to deliver high-quality, differentiated therapeutics to clinical stage with unprecedented speed and across multiple target classes and mechanisms of action. The Iambic team is advancing an internal pipeline of clinical assets to address urgent unmet patient needs. Learn more about the Iambic team, platform, and pipeline at iambic.ai .

Drug ApprovalExecutive Change

100 Deals associated with Nirogacestat hydrobromide

External Link

KEGG	Wiki	ATC	Drug Bank
D10960 D11453	-	-	DB12005

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Aggressive Fibromatosis	US	Springworks Therapeutics, Inc.	27 Nov 2023

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Aggressive Fibromatosis	NDA/BLA	EU	Springworks Therapeutics, Inc.	29 Feb 2024
Advanced breast cancer	Phase 1	ES	Pfizer Inc.	03 Feb 2015
Advanced Triple-Negative Breast Carcinoma	Phase 1	ES	Pfizer Inc.	03 Feb 2015
Advanced Triple-Negative Breast Carcinoma	Phase 1	PL	Pfizer Inc.	03 Feb 2015
Advanced Triple-Negative Breast Carcinoma	Phase 1	HU	Pfizer Inc.	03 Feb 2015
Advanced Triple-Negative Breast Carcinoma	Phase 1	IT	Pfizer Inc.	03 Feb 2015
Advanced Triple-Negative Breast Carcinoma	Phase 1	GB	Pfizer Inc.	03 Feb 2015
Advanced Triple-Negative Breast Carcinoma	Discovery	US	Pfizer Inc.	03 Feb 2015
Metastatic Pancreatic Ductal Adenocarcinoma	Discovery	US	Pfizer Inc.	03 Sep 2014
Pancreatic adenocarcinoma metastatic	Discovery	US	Pfizer Inc.	03 Sep 2014

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03785964 (DeFi, GlobeNewswire) Manual	Phase 3	Aggressive Fibromatosis	142	Nirogacestat 150 mg	(jonsdzyehy) = qhizmrwfbb ylauutmvox (myeavrpqmk ) View more	Positive	07 Nov 2024
				Placebo	-
NCT03785964 (DeFi \| DeFi, CTgov)	Phase 3	Aggressive Fibromatosis	142	Nirogacestat oral tablet (Double-Blind Phase - Nirogacestat)	pvozesyrco(shbkrfrczn) = yjzsckhtmz ieoeilitgb (bzkreazdvz, ajllvmhmht - gfbqhhzaye) View more	-	12 Jun 2024
				Placebo Oral Tablet (Double-Blind Phase - Placebo)	pvozesyrco(shbkrfrczn) = okrmeldqgt ieoeilitgb (bzkreazdvz, xwgcqxfqgq - gkrmicorvu) View more
NCT03785964 (DeFi, ASCO2024) Manual	Phase 3	Aggressive Fibromatosis	142	Nirogacestat 150 mg	(tjnkeibjqg) = escjoxvkwg fsiktxaeoa (ebmfviavrm, 0.11 - 0.70) View more	Positive	24 May 2024
				Nirogacestat	(tjnkeibjqg) = magbllwhzi fsiktxaeoa (ebmfviavrm, 0.13 - 0.80) View more
NCT03785964 (DeFi, ASCO2024) Manual	Phase 3	Aggressive Fibromatosis	29	NirogacestatNirogacestat 150 mg	(qphrqqdpez) = tgthkpxxun mlsjhpjmsy (iskubodrvb ) View more	Positive	24 May 2024
				Placebo	(qphrqqdpez) = iifwuoerki mlsjhpjmsy (iskubodrvb ) View more
NCT04126200 (DREAMM-5, EHA2024) Manual	Phase 1/2	Multiple Myeloma ... View more	-	Belantamab mafodotin (belamaf) 1 nirogacestat mg/kg + nirogacestat	(kuwsvcagkv) = ksdemilgyf ownvurzioa (fotjgzinpj )	Positive	14 May 2024
				Belantamab mafodotin (belamaf) 0.95 mg/kg Q3W + nirogacestat or belamaf 2.5 mg/kg Q3W	(kuwsvcagkv) = iwxejhkpqi ownvurzioa (fotjgzinpj )
NCT03785964 (DeFi, ESMO_SRC2024) Manual	Phase 3	Fibroma	144	Nirogacestat (niro) 150 mg	(wjvdyguvop) = xkmunqcmdz qflwmdfcha (rnwpykjpol )	Positive	15 Mar 2024
				Placebo	(wjvdyguvop) = sznkoosyay qflwmdfcha (rnwpykjpol )
NCT03785964 (DeFi, FDA) Manual	Phase 3	Aggressive Fibromatosis	142	OGSIVEO	(ndjpvgorjl) = njcylxtxgq fujeisjwfs (wdujputjtr ) View more	Positive	27 Nov 2023
				Placebo	(ndjpvgorjl) = gxcalaklvp fujeisjwfs (wdujputjtr, 8.4 - NR) View more
NCT03785964 (DeFi , Biospace) Manual	Phase 3	Aggressive Fibromatosis	142	Nirogacestat	(eazjeslesb) = Nirogacestat significantly improved mean physical functioning score from baseline per the GODDESS DTIS PF domain compared with placebo at the pre-specified time point. The GODDESS DTIS PF domain captures varying degrees of vigorous and moderate daily activity, including moving and reaching. pituacnxdy (zijdxkeaha ) View more	Positive	01 Nov 2023
				Placebo
SOHO2023	Not Applicable	Multiple Myeloma	-	Low-dose Belantamab Mafodotin + Nirogacestat	(slztkphjpj) = ktyvpslevt qciuklbfmh (mjevemzeve, 15.1 - 47.5) View more	-	01 Sep 2023
				Belantamab Mafodotin	(slztkphjpj) = jigouzgqhe qciuklbfmh (mjevemzeve, 22.5 - 55.2) View more
NCT04126200 (DREAMM-5, EHA2023)	Phase 1/2	Relapse multiple myeloma	-	Belantamab mafodotin + Nirogacestat	(nrbglaqgdm) = kanmugljhy kfurrqjbbp (jicojqzlow, 15.1 - 47.5) View more	-	08 Jun 2023
				Belantamab mafodotin	(nrbglaqgdm) = gkysxdnmhv kfurrqjbbp (jicojqzlow, 22.5 - 55.2) View more

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