On October 7, 2021 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported two poster presentations with new preclinical data for CA-4948, a first-in-class small molecule IRAK4 inhibitor, at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual Conference on Molecular Targets and Cancer Therapeutics (Press release, Curis, OCT 7, 2021, View Source [SID1234590924]).

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"In ongoing Phase 1 clinical trials, CA-4948 has already demonstrated anti-tumor activity in non-Hodgkin’s lymphoma, acute myeloid leukemia and myelodysplastic syndromes. New preclinical data presented at AACR (Free AACR Whitepaper)-NCI-EORTC today support the potential of CA-4948 in additional hematologic cancers," said James Dentzer, President and Chief Executive Officer of Curis.

"Notably, these new preclinical data indicate that CA-4948 is synergistic with small molecules targeting BCR signaling, including both idelalisib and ibrutinib, and suggest it may help overcome or reduce secondary resistance to these therapies in marginal zone lymphoma. In addition, these data demonstrate that CA-4948 can cross the blood brain barrier and improve survival, in a dose-dependent manner, providing additional preclinical support for the study of CA-4948 in patients with primary central nervous system (pCNS) lymphoma, one of the most aggressive forms of lymphoma and a clear area of unmet need for patients." Mr. Dentzer added.

Details of the presentations are as follows:

Title: Pharmacological inhibition of IRAK-4 with CA-4948 is beneficial in marginal zone lymphoma models with secondary resistance to PI3K and BTK inhibitors
Author: Francesca Guidetti, Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland
Poster Number: P073

Title: The IRAK4 inhibitor CA-4948 demonstrates antitumor activity in a preclinical model of CNS lymphoma
Author: Christina A. von Roemeling, Ph.D., Research Associate, UF Brain Tumor Immunotherapy Program, Department of Neurosurgery, McKnight Brain Institute, University of Florida
Poster Number: P243
Additional meeting information can be found on the AACR (Free AACR Whitepaper) website at:
View Source

The presentations will also be available under "Posters and Presentations" in the Pipeline: CA-4948 section of the Company’s website at www.curis.com

About CA-4948

CA-4948 is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with AML and MDS. Third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutations such as SF3B1 and U2AF1.

On October 7, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that XMT-2056, its first Immunosynthen STING-agonist ADC candidate, targets a novel epitope of human epidermal growth factor receptor 2 (HER2) and presented new preclinical data during a plenary session at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Triple Meeting) (Press release, Mersana Therapeutics, OCT 7, 2021, View Source [SID1234590939]).

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"Previously, across multiple targets and models, we demonstrated that our Immunosynthen ADCs can stimulate the innate immune system in a targeted manner in both tumor cells and tumor-resident myeloid cells – a "one-two punch" resulting in robust efficacy. New head-to-head preclinical data comparing XMT-2056 to TLR7/8-agonist ADC and systemically-administered STING agonist benchmarks further supports the potential advantages of XMT-2056 to offer greater efficacy and a wider therapeutic index," said Timothy B. Lowinger, PhD, Chief Science and Technology Officer of Mersana Therapeutics. "In addition, new data with XMT-2056 in combination with trastuzumab supports our rationale for selecting an antibody that recognizes a novel epitope of HER2, providing broad combination potential with approved and investigational HER2 therapies."

"STING is a fundamental mechanism yet approaches to date have been unsuccessful at stimulating the innate immune system in a targeted manner. Our Immunosynthen platform not only has the potential to address this limitation but also is designed to allow us to extend our ADC development efforts beyond cytotoxic payloads, which we believe represents a significant advancement in the ADC field," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "We are particularly excited about the potential of XMT-2056 to offer a novel approach to the treatment of HER2-expressing tumors both as a single agent and in combination."

Previously reported preclinical data suggest that XMT-2056 offers a highly differentiated approach, enabling tumor-targeted delivery of a STING agonist with improved efficacy and tolerability over a systemically-administered STING agonist benchmark. In vitro and in vivo studies demonstrate that STING-agonist ADCs activate the STING pathway in both tumor-resident immune cells and tumor cells, offering the potential for an increased therapeutic index and an advantage over other innate immune activating pathways.

The Company has evaluated Immunosynthen ADCs across a wide range of antibodies, targets, tumor models and mouse strains and observed broad efficacy and consistent results demonstrating target-dependent anti-tumor effects and has selected HER2 as the first target for clinical evaluation with XMT-2056. The Company developed a differentiated anti-HER2 antibody that binds a novel epitope distinct from that of trastuzumab and pertuzumab, providing the opportunity for combinations with these well-established anti-HER2 therapies.

New preclinical data presented today at the Triple Meeting include:

XMT-2056 demonstrated increased efficacy in both high and low HER2 SCID mouse models in comparison to benchmark agents such as a trastuzumab-TLR7/8 agonist ADC as well as a small molecule systemically-administered STING agonist.
XMT-2056 showed excellent in vivo efficacy as a single agent in a SKOV3 HER2 high model and this efficacy is further enhanced by combining XMT-2056 with a 3 mg/kg dose of trastuzumab.
XMT-2056 was generally well-tolerated in NHP studies with no clinical signs and no adverse findings in clinical pathology or histopathology after single and repeat IV doses of 9 mg/kg, at exposures far exceeding those necessary for efficacy in mouse models, indicating the potential for a wide therapeutic index.

On October 7, 2021 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported the presentation of preclinical data characterizing the mechanism of action of EPI-7386, ESSA’s lead product candidate for the treatment of prostate cancer (Press release, ESSA, OCT 7, 2021, View Source [SID1234590962]). The data include the results of nuclear magnetic resonance (NMR) studies which confirm the binding of the compound to the N-terminal domain (NTD) of the androgen receptor (AR), a region not currently targeted by other antiandrogen therapies. Data were presented in a virtual video poster format at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper), National Cancer Institute (NCI), and European Organisation for Research and Treatment of Cancer (EORTC) Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place virtually from October 7-10, 2021.

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The virtual poster presentation, titled, "Comprehensive preclinical characterization of the mechanism of action of EPI-7386, an androgen receptor N-terminal domain inhibitor," will be presented and available for viewing starting October 7, 2021 at 9:00 a.m. ET.

The preclinical data confirm EPI-7386’s target engagement with the NTD of the AR through multiple studies:

Three separate orthogonal NMR approaches confirm that EPI-7386 binds to the Tau5 region of the NTD
Cellular thermal shift assays (CETSA) confirm engagement of EPI-7386 with both full length AR (AR-FL) and AR-V567es, a splice variant lacking the ligand-binding domain (LBD)
Gene expression driven by the AR splice variant, AR-V567es, can be inhibited by EPI-7386 whereas enzalutamide and darolutamide, which bind to the LBD, cannot inhibit AR-V567es-driven gene expression
Chromatin immunoprecipitation sequencing (ChIP-Seq) data indicate that EPI-7386 inhibits androgen-induced changes at the AR cistrome and when combined with enzalutamide, can completely abrogate genome-wide androgen-induced AR binding
"We are excited by the data presented today, which support ESSA’s novel approach to prostate cancer by definitively demonstrating that EPI-7386 binds to the N-terminal domain of the androgen receptor—the primary driver of prostate cancer growth," said Dr. David R. Parkinson, M.D., President and Chief Executive Officer of ESSA Pharma Inc. "Through this unique mechanism of AR inhibition, EPI-7386 can inhibit AR-driven biology in both full length and splice variant-driven prostate cancer models. Additionally, the data demonstrate that the combination of EPI-7386 with enzalutamide results in complete inhibition of genome-wide androgen-induced AR binding, supporting the rationale for our upcoming Phase 1/2 combination trials of EPI-7386 with approved antiandrogens in patients with metastatic castration-resistant prostate cancer."

The poster is available on the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual International Conference website and on the "Events & Presentations" section of the Company’s website at www.essapharma.com.

On October 7, 2021 Amgen (NASDAQ: AMGN) and Neumora Therapeutics, Inc. (Neumora), a clinical-stage biopharmaceutical company pioneering precision medicines for brain diseases, reported a strategic collaboration to advance neuroscience discovery, development and commercialization (Press release, Amgen, OCT 7, 2021, View Source [SID1234590983]). The companies will collaborate on programs by applying Neumora’s proprietary precision neuroscience platform to insights generated by Amgen’s deCODE genetics and human data research capabilities. In addition, Neumora has received a $100 million equity investment from Amgen and acquired exclusive global rights to develop and commercialize Amgen programs targeting casein kinase 1 delta and glucocerebrosidase for neurodegenerative diseases.

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Neumora leverages proprietary multimodal capabilities and technologies to integrate advanced computational data science with R&D to increase the probability of success of drug development in brain diseases. Neumora’s precision neuroscience platform focuses on the creation of Data Biopsy Signatures to deconvolve the complex systems that drive brain diseases and connect the signatures to clinically meaningful measures to inform the development of therapeutics for an enriched patient population, or Precision Phenotypes.

Amgen’s deCODE genetics subsidiary is a global leader in analyzing and understanding human health and disease and has been at the forefront of the analysis of human data to enhance drug discovery and development. By leveraging these platform technologies and the complementary capabilities of both companies, the collaboration aims to discover unique and unprecedented insights into brain diseases across neuropsychiatric and neurodegenerative diseases, including schizophrenia and amyotrophic lateral sclerosis (ALS), ultimately leading to effective therapeutics targeted at patients most likely to respond to treatment.

"Our collaboration with Neumora leverages both our unique capabilities from deCODE and Neumora’s focus and expertise in brain diseases to discover and develop potentially best-in-class precision therapies," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Although Amgen is not currently engaged in neuroscience research and early development internally, this approach addresses our commitment to remain engaged in neuroscience through external collaborations, and we are excited to work with Neumora to propel R&D for brain diseases into the future and advance promising new medicines."

"This partnership with Amgen underscores the vast potential of precision drug development for brain diseases; insights generated by deCODE will further enhance Neumora’s data-driven precision medicine approach," said Paul L. Berns, co-founder, chairman and chief executive officer at Neumora. "We are also excited to expand our pipeline with potential best-in-class programs targeting casein kinase 1 delta and glucocerebrosidase for neurodegenerative diseases. Neumora is poised to become a pioneer in precision drug development for brain diseases and we look forward to working with Amgen to advance promising new medicines for patients in need of better treatment options."

About deCODE Genetics
Based in Reykjavik, Iceland, deCODE is a global leader in analyzing and understanding the human genome. Using its unique expertise in human genetics combined with growing expertise in transcriptomics and population proteomics and vast amount of phenotypic data, deCODE has discovered risk factors for dozens of common diseases and provided key insights into their pathogenesis. The purpose of understanding the genetics of disease is to use that information to create new means of diagnosing, treating and preventing disease. deCODE is a wholly-owned subsidiary of Amgen.

On October 7, 2021 Calliditas Therapeutics AB (Nasdaq: CALT, Nasdaq Stockholm: CALTX) ("Calliditas") reported that the company now controls 100% of the share capital of Genkyotex SA ("Genkyotex"), after the completion of a centralized squeeze out offer to all minority shareholders (Press release, Calliditas Therapeutics, OCT 7, 2021, View Source [SID1234590894]).

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Genkyotex’s lead product candidate, setanaxib, is a first-in-class NOX inhibitor that targets NOX 1 and NOX 4, which are major drivers of fibrogenesis in multiple organs. In Q4 2021, Calliditas plans to initiate a 52-week, randomized, placebo-controlled, double-blind, trial with an adaptive phase 2b/3 design with setanaxib in 318 patients with primary biliary cholangitis (PBC). As previously announced in August 2021, Calliditas received FDA fast track designation for setanaxib in PBC. Calliditas will also initiate a Phase 2 proof-of-concept study in head and neck cancer in 2021, which will investigate the administration of setanaxib in conjunction with immunotherapy targeting cancer associated fibroblasts (CAFs).

"We are delighted to have completed our acquisition of Genkyotex, which means that we now can fully integrate the business and thereby leverage the platform optimally", said CEO Renée Aguiar-Lucander.

Subsequent to the squeeze-out, Genkyotex has become a wholly owned subsidiary of Calliditas and have been delisted from the Euronext stock exchanges.

The information was sent for publication, through the agency of the contact persons set out above, on October 7, 2021 at 8:00 a.m. CET.