On March 8, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that pre-clinical data on JZP815, an investigational, next-generation pan-RAF kinase inhibitor, will be presented as a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting from April 8-13, 2022 (Press release, Jazz Pharmaceuticals, MAR 8, 2022, View Source [SID1234609726]).

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"Together with our pre-clinical collaboration partner, Redx Pharma, we look forward to presenting at AACR (Free AACR Whitepaper) our first pre-clinical data on JZP815, which demonstrated that it selectively and potently inhibits mutant A, B and CRAF kinases, and demonstrated anti-tumor activity in RAS- and RAF-mutant xenograft models," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "The pan-RAF inhibitor program is part of a novel class of next generation precision oncology therapies that has the potential to benefit cancer patients with high unmet needs in multiple different solid tumors. We look forward to progressing JZP815 to the clinic to further evaluate the benefit it may have for appropriate patients."

The Jazz presentation abstract – titled, "JZP815, a potent and selective pan-RAF inhibitor, demonstrates efficacy in RAF and RAS mutant tumor pre-clinical models" – and the AACR (Free AACR Whitepaper) 2022 Annual Meeting details are available here.

Activation of the mitogen-activated protein kinase (MAPK) pathway by oncogenic mutations in RAS and RAF is a frequent driver of cancer. Targeting specific components of the pathway can be a precise and rational route to deliver benefits to cancer patients with high unmet needs. The RAF kinase proteins (ARAF, BRAF, CRAF) are core pathway components that mediate MAPK signaling. Mutations in these critical signaling proteins leads to constitutive activation of the MAPK pathway and tumor growth.

JZP815 is an investigational, pre-clinical stage, next-generation pan-RAF kinase inhibitor that was discovered and developed using state-of-the-art screening methodologies and medicinal chemistry. JZP815 is not currently approved for use anywhere in the world.

Jazz acquired JZP815 from Redx Pharma, and the two companies are collaborating on this pre-clinical research. Jazz plans to submit an IND for JZP815 this year. JZP815 is part of Jazz’s growing early-stage R&D pipeline focused on precision oncology in solid tumors.

On March 8, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported the publication of two abstracts that have been accepted for poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is taking place both virtually and in-person at the Ernest N. Morial Convention Center in New Orleans, Louisiana from April 8-13, 2022 (Press release, Cardiff Oncology, MAR 8, 2022, View Source [SID1234609725]).

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The full texts of the published abstracts can be found on the AACR (Free AACR Whitepaper) Annual Meeting website. Details on the corresponding posters are shown below.

Poster Title:

Biomarkers of response to abiraterone and the polo-like kinase 1 (PLK1)
inhibitor onvansertib in metastatic castration resistant prostate cancer
(mCRPC) patients

Session Title:

Biomarkers Predictive of Therapeutic Benefit 1

Session Date:

April 11, 2022

Session Start Time:

9:00 AM CT

Location:

Poster Section 30

This abstract describes genomic and transcriptomic analyses from the ongoing Phase 2 trial of onvansertib in combination with Zytiga (abiraterone)/prednisone in mCRPC patients with early abiraterone resistance. Collectively, these analyses suggest that alterations in PTEN and MTOR, two key genes of the PI3K signaling pathway, are potential biomarkers for sensitivity to onvansertib-abiraterone combination therapy in mCRPC patients with early abiraterone-resistance.

Poster Title:

Combining PARP inhibition with the polo-like kinase 1 (PLK1)
inhibitor onvansertib overcomes PARP inhibitor resistance

Drug Resistance and Reversal of Resistance

Session Date:

April 12, 2022

Session Start Time:

1:30 PM CT

Location:

Poster Section 22

This abstract includes preclinical data that demonstrate the potent anti-tumor activity of onvansertib combined with the PARP inhibitor olaparib in olaparib-resistant ovarian cancer models. Additional preclinical studies are ongoing to further assess the potential of the onvansertib-olaparib combination in models of ovarian, prostate, pancreatic and breast cancer.

On March 8, 2022 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported that the data from its oncology programs will be presented at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place April 8-13 in New Orleans, U.S (Press release, Ryvu Therapeutics, MAR 8, 2022, View Source [SID1234609724]).

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Posters to be presented at the conference will include data from RVU120, a CDK8/CDK19 inhibitor program targeting hematologic and solid tumors, and data from an MTA-cooperative PRMT5 inhibitor program.

"We are excited to share the recent preclinical data in breast cancer from our most advanced oncology program, RVU120. This selective inhibitor of CDK8/CDK19 is currently in Phase 1b clinical development for the treatment of acute myeloid leukemia or high-risk myelodysplastic syndromes, as well as in patients with metastatic or advanced solid tumors, and has already delivered promising data," said Krzysztof Brzózka, Chief Scientific Officer at Ryvu Therapeutics. "We have also made rapid progress in our MTA-cooperative PRMT5 inhibitor program, and we look forward to sharing these updates with the scientific community," adds Dr. Brzózka.

Abstract/Poster Details:

Title: RVU120, a selective CDK8/CDK19 inhibitor, demonstrates efficacy against hormone-independent breast cancer cells in vitro and in vivo
Abstract Number: 2647
RVU120 is a specific, low nM, selective inhibitor of CDK8/CDK19, currently being tested in a first-in-human Phase Ib clinical trial in patients with metastatic or advanced solid tumors progressing from previous lines of therapy (ClinicalTrials.gov: NCT05052255). Studies on a panel of cell lines representing various subtypes of breast cancer revealed that TNBC cells were highly sensitive to RVU120. Molecular profiling of responder cells indicated high enrichment for mesenchymal stem cells-like subtype. Single agent efficacy of RVU120 has been confirmed in subcutaneous TNBC xenograft models in vivo at well tolerated doses. Overall, these studies provide rationale for further development of RVU120 in TNBC patients.
Session Title: Novel Targets and Pathways
Session Date and Time: Tuesday Apr 12, 2022 9:00 AM – 12:30 PM
Location: Poster Section 24

Title: Discovery of novel MTA-cooperative PRMT5 inhibitors as a targeted therapeutic for MTAP deleted cancers
Abstract Number: 1117
Targeting PRMT5 in MTAP-deleted tumors in a synthetic lethal approach represents a promising antitumor strategy across many tumor types. Ryvu has identified a series of MTA-cooperative PRMT5 inhibitors with good drug-like physicochemical properties and block methyltransferase activity with nanomolar IC50 values. Ryvu compounds selectively inhibit the growth of MTAP deleted cancer cells in prolonged 3D culture, which strongly correlates with inhibition of PRMT5-dependent protein symmetric demethylation (SDMA) in those cells. Overall, these studies provide the rationale for the further optimization of chemical series towards a clinical candidate.
Session Title: Drug Targets
Session Date and Time: Monday Apr 11, 2022 1:30 PM – 5:00 PM
Location: Poster Section 23

Title: Trials in Progress – RVU120 SOL-021: An open-label, single agent, Phase I/II trial of RVU120 (SEL120) in patients with relapsed/refractory metastatic or advanced solid tumors
Abstract Number: 8023
SOL-021 is a Phase I/II clinical trial of RVU120 in patients with metastatic or advanced solid tumors, who have exhausted available treatments, currently ongoing in Poland and Spain (NCT05052255). The study is designed in 2 parts: Part 1 follows a 3+3 dose escalation design, and the primary objectives are to characterize the safety and tolerability of RVU120 as a single agent in patients with different tumors types and determine the RP2D. Part 2 will primarily explore the anti-tumor activity of RVU120 as a single agent in different patient populations. As of a data cutoff of 11 Feb 2022, 5 patients have been enrolled in Part 1 of the study and no DLTs have been observed.
This Trials in Progress abstract is published in cooperation with the Early Clinical Trials Centre and Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland; Early Drug Development Unit (UITM) Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Barcelona, Spain; Dep. of Internal Medicine III, Univ. Clinic, Bonn, Germany and Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Session Title: Phase II Trials in Progress
Session Date and Time: Monday Apr 11, 2022 9:00 PM – 12:30 PM
Location: Poster Section 34

About AACR (Free AACR Whitepaper) Annual Meeting

The AACR (Free AACR Whitepaper) Annual Meeting program covers the latest discoveries across the spectrum of cancer research—from population science and prevention, to cancer biology, translational, and clinical studies; to survivorship and advocacy—and highlights the work of the best minds in research and medicine from institutions all over the world. Additional information is available on the AACR (Free AACR Whitepaper) conference website View Source

On March 8, 2022 Theseus Pharmaceuticals, Inc. (NASDAQ: THRX) (Theseus or the Company), a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients through the discovery, development and commercialization of transformative targeted therapies, reported that the Company will present a poster highlighting the characterization of potent and selective next-generation EGFR inhibitors at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, being held April 8-13, 2022 in New Orleans, Louisiana (Press release, Theseus Pharmaceuticals, MAR 8, 2022, View Source [SID1234609723]).

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Presentation details:
Abstract Title: Discovery of potent and selective next-generation EGFR inhibitors with activity against single, double, and triple mutant EGFR variants including T790M and C797S
Abstract Number: 3342
Presenter: Wei-Sheng Huang, Ph.D., Vice President of Chemistry
Session Date and Time: Tuesday, April 12th, 1:30pm-5pm CT

The presentation will detail the characterization of compounds that potently inhibit the kinase activity, both in vitro and in vivo, of single, double, and triple mutant EGFR variants including T790M and C797S, with selectivity over wild-type EGFR and the ability to penetrate the central nervous system. These variants comprise all major classes of EGFR activating and resistance mutations that contribute to later-line clonal heterogeneity in patients who have been failed by current approved therapies.

EGFR activating mutations are observed in 10-50 percent of non-small cell lung cancer (NSCLC) patients and are initially sensitive to first, second, and third generation EGFR inhibitors. However, on-target resistance is observed in a substantial percentage of patients, with T790M and C797S mutations observed most frequently.

On March Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), a development-stage biotechnology company pioneering the first systematic approach to use mRNA therapeutics as a new class of programmable epigenetic medicines by leveraging its OMEGA Epigenomic Programing platform, reported that it will present preclinical data for OTX-2002, the Company’s lead drug candidate for the treatment of hepatocellular carcinoma (HCC), at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place in New Orleans, Louisiana, April 8-13, 2022 (Press release, Omega Therapeutics, MAR 8, 2022, View Source [SID1234609722]).

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"These preclinical data highlight the potential of epigenetic modulation of the c-MYC (MYC) oncogene as a promising new approach for the treatment of hepatocellular carcinoma (HCC), where MYC over expression is associated with aggressive disease in up to 70% of HCC cases," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "While MYC represents an attractive therapeutic target, it has historically been considered undruggable, due to the consistent failure of current modalities to inhibit MYC directly or indirectly. We look forward to sharing these data that support the potential of epigenetic modulation using our platform to systematically control the underlying biology of gene expression and remain on track to file an Investigational New Drug application for OTX-2002 in the first half of 2022."

Details for the AACR (Free AACR Whitepaper) Annual Meeting 2022 poster presentation are as follows:

Title: Epigenetic modulation of the MYC oncogene as a potential novel therapy for HCC
Abstract #: 2629
Date and Time: Tuesday, April 12, 2022 at 9:00 a.m. through 12:30 p.m. CDT

The poster will be posted to our website at View Source at the same time as the presentation.

About OTX-2002

OTX-2002 is a first-in-class Omega Epigenomic Controller in development for the treatment of hepatocellular carcinoma (HCC). OTX-2002 is designed to modulate levels of c-MYC (MYC) expression by utilizing targeted mRNA-encoded proteins to mediate epigenetic regulation while potentially overcoming MYC auto regulation. The MYC oncogene is associated with aggressive disease in up to ~70% of patients with HCC. Omega is currently evaluating OTX-2002 in Investigational New Drug (IND)-enabling studies.