On March 08, 2022 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is biologically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics for the treatment of cancer and autoimmune diseases, reported that the Company will present updated results from its single-agent Phase 1 clinical trial of RTX-240 in advanced solid tumors in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held from April 8-13, 2022 at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, Rubius Therapeutics, MAR 8, 2022, View Source [SID1234609662]). The Company also plans to host a webcast to discuss the results from the single-agent Phase 1 trial of RTX-240 in solid tumors and AML on April 8, 2022, at 1:15 p.m. ET, following the release of the AACR (Free AACR Whitepaper) abstracts.

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"In March 2021, we reported initial results from the RTX-240 Phase 1/2 clinical trial which established clinical proof of concept of RTX-240 in advanced solid tumors and clinical validation of the RED PLATFORM, unlocking the potential of our entire oncology platform," said Pablo J. Cagnoni, M.D., president and chief executive officer of Rubius Therapeutics. "As part of our poster at AACR (Free AACR Whitepaper) and planned company webcast, we look forward to presenting updated clinical results from the ongoing RTX-240 trial in patients with solid tumors and AML, including additional safety, efficacy and pharmacodynamic data from patients enrolled at higher dose levels and follow up from the patients who were included in the March 2021 announcement. We also intend to share our expected next steps for Phase 2 clinical development."

Abstract Title: Phase 1 Trial of RTX-240, Allogeneic Red Blood Cells Engineered to Express 4-1BBL and Trans-Presented IL-15, in Patients with Advanced Solid Tumors
Session Title: Phase I Clinical Trials 2
Session Date and Time: Tuesday, April 12, 2022, 9:00 a.m. – 12:30 p.m. ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 33
Poster Board Number: 12
Abstract Number: CT187

Investor Webcast
The Company plans to host a webcast on April 8, 2022, at 1:15 p.m. ET, following the release of the AACR (Free AACR Whitepaper) abstracts. Details will be available on the Investors & Media section of the Rubius website.

About RTX-240
RTX-240, Rubius Therapeutics’ lead oncology program, is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to broadly stimulate the immune system by activating and expanding both NK and memory T cells to generate a potent anti-tumor response.

About the RTX-240 Clinical Trial
This is a Phase 1/2 open label, multicenter, multidose, first-in-human dose-escalation and expansion study designed to determine the safety and tolerability, pharmacokinetics, maximum tolerated dose and a recommended Phase 2 dose and dosing regimen of RTX-240 in adult patients with relapsed/refractory or locally advanced solid tumors or with relapsed/refractory acute myeloid leukemia. The trial will also assess the pharmacodynamics of RTX-240 measured by changes in T and NK cell number and function relative to baseline and anti-tumor activity. The study will include a monotherapy dose escalation phase followed by an expansion phase in specified tumor types during the Phase 2 portion of the trial.

On March 8, 2022 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision oncology biopharmaceutical company, reported that it will present the first data from its preclinical synthetic lethality pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, being held April 8-13, 2022, in New Orleans, LA (Press release, Calithera Biosciences, MAR 8, 2022, View Source [SID1234609679]).

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The accepted poster will detail Calithera’s discovery of a novel series of vacuolar protein sorting-associated protein 4A (VPS4A) inhibitors that are currently advancing through lead optimization. VPS4A and VPS4B are paralog ATPases essential for remodelling intracellular organelle membranes. Membrane remodelling is an essential cellular function and loss of function of both VPS4 paralogs is lethal to cells. The preclinical data demonstrate that VPS4A genetic inhibition in cell lines with loss of VPS4B preferentially showed profound death in cancer cells.

"The data being shared at the AACR (Free AACR Whitepaper) annual meeting suggest that inhibition of VPS4A is a promising approach to treat cancers across a wide variety of cancer types that harbor VPS4B deletions. We believe the discovery of this series of VPS4A inhibitors is a significant step forward in our efforts to expand our pipeline of targeted therapies to ultimately treat patients with high unmet need," said Susan Molineaux, chief executive officer of Calithera. "Additionally, we are excited about the progress we have made in advancing these discoveries as we focus on lead optimization. Synthetic lethal cancer therapies are highly promising, and we look forward to contributing to this rapidly advancing field with this novel mechanism."

Calithera is building a robust preclinical pipeline of additional synthetic lethality targets with a continuing focus on paralog genes. Gene paralog pairs represent a promising class of synthetic lethal cancer targets. When a tumor cell loses one paralog, the cell is dependent on the second paralog to carry out an essential cellular process, since loss of both paralogs leads to tumor cell death. Calithera researchers have confirmed VPS4A and VPS4B as synthetic lethal paralog pairs, noting that both homozygous and heterozygous loss of VPS4B in cancer cells makes them vulnerable to VPS4A inhibition. VPS4B is lost in a heterozygous fashion in the majority of colorectal cancer, pancreatic ductal adenocarcinoma, ovarian, esophageal and head & neck cancers and is deleted in large numbers of other tumor types. At AACR (Free AACR Whitepaper) 2022, Calithera will report the discovery of a series of novel, small-molecule VPS4A inhibitors which have potential in the treatment of VPS4B-deleted tumors.

Details of the abstract accepted for presentation at AACR (Free AACR Whitepaper) 2022 (#1816) are as follows:

Title: Identification of novel VPS4A inhibitors for the treatment of VPS4B-deleted cancers
Session Category: Experimental and Molecular Therapeutics/Drug Targets
Session Title: Drug Targets
Date and Time: Monday Apr 11, 2022, 1:30 PM – 5:00 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 23
Poster Board Number: 14
Permanent Abstract Number: 1816
Presenter: Meredith Kuo, Ph.D.
This abstract is currently available on the AACR (Free AACR Whitepaper) website, and the poster will be available on Calithera’s website on April 8, 2022.

On March 8, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for blood cancers and serious blood diseases, reported that the company will host a conference call and live audio webcast on Tuesday, March 15, 2022, at 8:00 a.m. ET to review its fourth quarter and full year 2021 financial results and provide an update on the company (Press release, Gamida Cell, MAR 8, 2022, View Source [SID1234609695]).

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The webcast will be available on the "Investors & Media" section of the Gamida Cell website at www.gamida-cell.com. To participate in the live call, please dial 866-930-5560 (domestic) or 409-216-0605 (international) and refer to conference ID number 1696742. A replay of the webcast will be available approximately two hours after the event, for approximately 30 days.

On March 8, 2022 Exscientia (Nasdaq: EXAI) reported the acceptance of three abstracts for poster presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, being held April 8-13, 2022, at the Ernest N. Morial Convention Center in New Orleans, LA (Press release, Exscientia, MAR 8, 2022, View Source [SID1234609712]).

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"The abstracts highlighted at AACR (Free AACR Whitepaper) demonstrate the potential of our functional precision oncology tools to improve clinical and patient outcomes by guiding treatment and patient selection using a combination of AI and disease-relevant models," said Andrew Hopkins, DPhil., CEO and founder of Exscientia. "We believe these data demonstrate the exciting potential of our pipeline and further validate our translational research capabilities and AI-driven drug discovery platform as we continue in our efforts to deliver better molecules and identify promising therapeutic assets that have the best chance of clinical success."

Abstracts Accepted for Poster Presentation:

Title: Enriching for adenosine antagonist patient responses through deep learning
Session Title: Immunomodulatory Agents and Interventions
Abstract Number: #4150
Date/Time: Wednesday, April 13 / 9:00 AM – 12:30 PM CT

Translation of preclinical data to the clinical setting has been a persistent gap in successful drug discovery. In this study, researchers leveraged Exscientia’s AI-driven platform to develop patient gene signatures that could guide and better inform clinical study of new medicine candidates. By using deep learning driven image analysis, researchers are working towards identifying an adenosine-induced, tumour protective, immunosuppression biomarker to potentially improve the likelihood of clinical success for A2aR targeted therapies. Further, by leveraging patient material as well as baseline and treatment condition transcriptomics, Exscientia was able to model and functionally validate patient gene signatures to map the association of anti-cancer immune activity with the inhibition of adenosine signaling by EXS-21546, Exscientia’s clinical stage A2a antagonist, in development for the treatment of high adenosine signature cancers. These encouraging data suggest that stratification of patient gene signatures could be implemented in future studies of EXS-21546 to identify patients that may respond optimally to A2aR targeted therapies.

Title: AI-driven discovery and profiling of GTAEXS-617, a selective and highly potent inhibitor of CDK7
Session Title: Emerging New Anticancer Agents
Abstract Number: #3930
Date/Time: Wednesday, April 13 / 9:00 AM – 12:30 PM CT

Historically, CDK7 inhibition, a validated target that has been shown to severely limit the ability of cancer cells to proliferate in vitro and in vivo, has been challenging to address due to side effect profiles from development candidates, possibly due to covalent binding mechanism of action or poor oral absorption. By leveraging AI models and active learning, Exscientia was able to design an orally bioavailable, highly potent and selective small-molecule antagonist of CDK7, GTAEXS-617, currently in IND-enabling studies as a potential treatment for transcriptionally addicted cancers, including ovarian and breast cancer. Preclinical data show that ‘617 has potent anti-proliferative activity in in vitro models of high-grade serous ovarian cancer (HGSOC) and triple negative breast cancer (TNBC), and potent anti-tumour activity in HGSOC and TNBC xenograft tumour-bearing mice, resulting in complete tumour regression. By leveraging Exscientia’s precision oncology platform, researchers examined the impact of ‘617 on primary patient ovarian cancer samples. On the platform, two response groups of the patient samples began to form, and researchers are continuing to investigate this phenomenon with the aim to define a patient selection biomarker to enrich patients more likely to respond to CDK7 inhibition. The AI-driven platform was able to improve upon historic design concerns with CDK7 inhibitors, including efflux and GI tract toxicity.

Title: Deep learning supported high content analysis of primary patient samples identifies ALK inhibition as a novel mechanism of action in a subset of ovarian cancers
Session Title: New Technologies for Drug Discovery
Abstract Number: #1893
Date/Time: Monday, April 11 / 1:30 PM – 5:00 PM CT

Targeted therapies are needed for patients suffering from a myriad of diseases, but preclinical drug discovery is often performed in murine models which are not human disease relevant and lack the microenvironment and heterogeneity of human biology. This study highlights the potential of Exscientia’s precision medicine platform to identify novel targets and targetable pathways using human disease relevant patient tissue models, which could have the potential to improve patient outcomes by uncovering clinical relevance at the target discovery stage. By evaluating malignant pleural effusion and ascites from 20 patients with ovarian cancer against greater than 80 small molecules using high content microscopy, researchers were able to identify a pathway containing anaplastic lymphoma kinase (ALK) as a potential novel target in a subset of ovarian cancer patient samples. These encouraging data support further research of patient-focused drug development using human disease relevant models and deep learning to better understand the target landscape for ovarian cancer and the potential for the development of novel therapeutic approaches.

On March 8, 2022 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 that it will present preclinical data for its first generation of androgen receptor (AR) N-terminal domain degraders at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, ESSA, MAR 8, 2022, View Source [SID1234609729]). The ANITen bAsed Chimera (ANITAC) degraders suppressed AR transcriptional activity and decreased the viability of prostate cancer cells in castration-resistant prostate cancer (CRPC) preclinical models. ANITAC degraders degraded full length, mutant and splice variant forms of AR that are expressed in CRPC patients.

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Poster presentation details are as follows:

Title: Androgen receptor (AR) N-Terminal Domain degraders can degrade AR full length and AR splice variants in CRPC preclinical models
Authors: Nan Hyung Hong, et al.
Abstract Number: 429
Session Title: Protein Degraders and Proteasome Inhibitors
Session Date and Time: Sunday, April 10, 2022 | 1:30 p.m. – 5:00 p.m. ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 26

The e-poster will be available to 2022 AACR (Free AACR Whitepaper) Annual Meeting attendees and on the Company’s website at www.essapharma.com on April 8, 2022, at 1:00 p.m. ET.