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Second Genome Presents Preclinical Data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Demonstrating that a Novel Peptide, SG-3-0020, Upregulates Co-stimulatory and Checkpoint Pathways

On October 7, 2021 Second Genome, a biotechnology company that leverages its proprietary platform sg-4sight to discover and develop precision therapies and biomarkers, reported that preclinical data demonstrating that the Company’s novel microbiome-derived peptide, SG-3-0020, can upregulate key co-stimulatory and checkpoint molecules on T cells (Press release, Second Genome, OCT 7, 2021, View Source [SID1234590963]). The data (poster P260) were presented at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC 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), held virtually on October 7-10, 2021.

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"Our findings that SG-3-0020 enhanced PD-1 expression and IFNg secretion by anti-CD3 activated human T cells in vitro provide a strong rationale for SG-3-0020’s potential future use in cancer therapies. Additionally, we are pleased to see these results provided additional validation of the advanced capabilities of sg-4sight, Second Genome’s proprietary platform, to identify targets for microbial peptides and proteins with potential therapeutic relevance in immuno-oncology," said Helena Kiefel, Ph.D., Head of Immuno-Oncology at Second Genome. "Given these promising preclinical data, we are looking to further develop SG-3-0020 with an experienced partner, as we continue to advance SG-3-00802, our lead immuno-oncology program for which we anticipate an IND submission in 2022 for SG-3-00802."

Using Second Genome’s large and curated microbiome database coupled with its proprietary bioinformatics and machine learning tools, the Company analyzed the genome of Bifidobacterium (B.) breve and B. longum for proteins which were potentially secreted and had unknown functions. 50 peptides were chemically synthesized and then screened in cell-based assays for T cell activation and cytokine secretion.

SG-3-0020, a novel B. breve-derived 42-aa peptide, stimulated secretion of effector cytokines by in vitro-cultured T cells (IFNg, TNF-a, IL-10 and IL-2) and increased the expression of PD-1 on both CD4+ and CD8+ T cells when stimulated with low-dose anti-CD3 antibody. Mass spec analysis showed that SG-3-05308, a variant of SG-3-0020, binds to a transmembrane glycoprotein of the immunoglobulin superfamily. Silencing this gene via CRISPR-Cas significantly decreased PD-1 levels, cell proliferation and IFNg production in human pan T cells.

The potency of SG-3-0020 was further optimized for binding to activated T cells through protein engineering. The peptide with the highest potency, SG-3-05429, was selected for further investigation of the mechanism by which binding of its glycoprotein target results in activation of downstream T cell signaling pathways.

The poster presentation will be available for on-demand viewing on 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) website and will also be made available on the Company’s website at View Source

ESSA Pharma Announces the Presentation of Preclinical Data Characterizing the Mechanism of Action of EPI-7386

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.

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.

Mirati Therapeutics to Collaborate with Sanofi on Phase 1/2 Study Evaluating Combination of adagrasib with a SHP2 Inhibitor in KRAS G12C-mutated Lung Cancer

On October 7, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported a non-exclusive clinical collaboration agreement with Sanofi to evaluate the combination of adagrasib, the Company’s investigational KRASG12C inhibitor, with Sanofi’s investigational SHP2 inhibitor SAR442720, also known as RMC-4630 (Press release, Mirati, OCT 7, 2021, View Source [SID1234590960]). The Phase 1/2 dose escalation and expansion study will evaluate the combination in patients with previously-treated non-small cell lung cancer (NSCLC) and KRASG12C mutations.

"Mirati is aggressively advancing a broad adagrasib development program, which includes pursuing novel combination approaches including through this collaboration with Sanofi," said Charles M. Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "There is strong scientific rationale for combining a SHP2 inhibitor with adagrasib, which may help optimize clinical outcomes for patients with KRASG12C-dependent tumors."

SHP2 is upstream of KRAS and mediates cellular signaling through the RAS/MAP kinase pathway and is frequently overactive in various types of cancer. KRASG12C inhibition and SHP2 inhibition have complementary mechanisms of action and have demonstrated additive anti-tumor activity in pre-clinical models.

Under the terms of the agreement, Sanofi will be responsible for sponsoring and operating the Phase 1/2 study, and jointly with Mirati, will oversee and share costs of the study.

About Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C mutated cancers, as the KRASG12C protein regenerates every 24−48 hours. Adagrasib is a being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

About SAR442720 (RMC-4630)

SAR442720 (RMC-4630) is a potent and orally bioavailable small molecule that is designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a central role in modulating cell survival and growth by transmitting signals from receptor tyrosine kinases to RAS. SAR442720 (RMC-4630) is the focus of an exclusive global development and commercialization agreement between Sanofi and Revolution Medicines.

ProfoundBio Announces Presentation on Novel, Proprietary Linker-Drug Technology to Enable Antibody-Drug Conjugates (ADCs) with an Expanded Therapeutic Window at the AACR-NCI-EORTC International Conference

On October 7, 2021 ProfoundBio reported that preclinical data from its novel, proprietary ADC technology platform are being presented at the 2021 Molecular Targets and Cancer Therapeutics conference hosted by the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC) (Press release, ProfoundBio, OCT 7, 2021, View Source [SID1234590959]). The presentation is entitled, "Novel Hydrophilic Drug Linkers Enable Exatecan-based Antibody-Drug Conjugates with Promising Physiochemical Properties and In Vivo Activity."

"Our platform enables us to develop ADCs that could otherwise not even be considered for development. By optimizing physiochemical properties, our platform enables the use of hydrophobic payloads at a drug to antibody ratio (DAR) up to 8, and potentially higher, while maintaining similar pharmacokinetics to unconjugated mAb, robust anti-tumor activity, and an acceptable safety profile," said Baiteng Zhao, PhD, Chief Executive Officer at ProfoundBio. "This technology has the potential to usher in a new generation of ADCs that will meaningfully help patients who have cancer."

Repare Therapeutics Issues Statement Regarding Inadvertent Issuance of Phase 1/2 TRESR RP-3500 Clinical Trial Abstract by the AACR-NCI-EORTC Virtual International Conference

On October 7, 2021 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported the following statement concerning the inadvertent issuance of an abstract by 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) ("ANE Conference") concerning an upcoming oral presentation of initial monotherapy clinical data from its ongoing Phase 1/2 clinical trial of RP-3500 (Press release, Repare Therapeutics, OCT 7, 2021, View Source [SID1234590957]):

"Repare was alerted to the ANE Conference’s inadvertent early issuance of an abstract highlighting the upcoming oral presentation of initial monotherapy clinical data from the Company’s ongoing Phase 1/2 clinical trial of RP-3500. The Abstract highlights results taken from a very early cutoff date for the ongoing study, currently in its Phase 1 portion. The oral presentation, which will be delivered by Dr. Timothy Yap, MBBS, Ph.D., FRCP, Medical Director, Institute for Applied Cancer Science, Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, Texas, and which is expect to take place on Friday, October 8, 2021 at 3:15 p.m. ET, will include both significantly more patient data as well as a later cut off date and consequent longer follow up."

Company Virtual Investor Webcast Event Details

The Company has also announced that it will host a virtual investor webcast on Friday, October 8, 2021 at 5:00 p.m. ET to further discuss the data, where Repare’s executive management team will be joined by Dr. Yap. This Company’s presentation will include additional updates from past the cutoff date for the ANE Conference presentation. The Company looks forward to both presentations and to sharing results from these substantial updates.

To join the Company’s live video webcast, go to the Investor section of the Company’s website at View Source The Webcast will begin at 5:00 p.m. ET on Friday, October 8, 2021. A webcast replay will also be archived for at least 30 days.

About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.