On April 11, 2022 Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vectored immunotherapies, reported encouraging new translational data obtained from the ongoing Phase 1 trial evaluating NOUS-209 (Press release, NousCom, APR 11, 2022, View Source [SID1234612021]). The data were presented yesterday in a Late Breaking session at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

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NOUS-209, Nouscom’s lead product, is an off-the-shelf cancer vaccine targeting 209 shared neoantigens. It is being investigated in a Phase 1 clinical trial, administered in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, for the treatment of Microsatellite Instable High (MSI-H) gastric, colorectal and gastro-esophageal junction solid tumors.

Previously presented interim clinical data of the combination (presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting in November 2021) highlighted promising early signs of clinical efficacy in 12 MSI-H patients.

The new translational data presented at AACR (Free AACR Whitepaper) 2022 further supported these findings and demonstrated NOUS-209 is safe, highly immunogenic with promising signs of clinical efficacy. Key findings were as follows:

Vaccine immunogenicity was demonstrated by ex-vivo IFN-ɣ ELISpot assay in 67% of patients in dose level 1 (n=3), and 100% (n=7) of patients in dose level 2.
In 3 patients with long term PRs whose pre/post treatment tumor biopsies were available, the intratumoral TCR repertoire was expanded and diversified post treatment with NOUS-209. Increased T effector memory post treatment was observed.
In one of these three patients, vaccine-induced neoantigen specific TCR was tracked from periphery in the tumor biopsy post NOUS-209 treatment.
Results indicate that neoantigen specific CD8+ T cells, induced by NOUS-209, expand and diversify only upon treatment with NOUS-209, and successfully infiltrate the tumor microenvironment to exert anti-tumor activity.
Marwan G. Fakih, M.D., Medical Oncology Specialist at City of Hope’s Duarte California, and Study investigator said: "While we have seen progress in the treatment options for MSI-High solid tumors in recent years, there remains a significant unmet need. It is therefore extremely encouraging to see these new translational Phase 1 data illustrating how NOUS-209 induces robust T cell expansion and TCR diversification in patients demonstrating durable clinical responses. I very much look forward to the full analysis of the Phase 1 results and further clinical development."

Dr. Elisa Scarselli, Chief Scientific Officer and Co-Founder of Nouscom, said: "The data, obtained from 12 metastatic MSI-H patients, highlights a common signature observed post vaccination in patients with durable clinical response. The signature is characterized by the TCR repertoire expansion and diversification in tumor infiltrating lymphocytes stimulated by vaccination with NOUS-209, together with a parallel increase of T cells with effector memory phenotype. Moreover, we were able to track vaccine induced T cells among those expanded post-treatment in the tumor of one of these patients.

"We look forward to building upon our compelling proof-of-concept data by leveraging important learnings from the ongoing trial to support the development of NOUS-209 as potentially the first neoantigen off-the shelf cancer vaccine targeting MSI-H tumors."

Poster Presentation Details:

Title: Characterization of immune correlates of clinical activity for NOUS-209, an Off-the-Shelf immunotherapy, with Pembrolizumab for treatment of tumors characterized by Microsatellite Instability (MSI).
The abstract is available here
About NOUS-209

NOUS-209 is an off-the-shelf immunotherapy for Microsatellite Instable High (MSI-H) tumors. MSI-H tumors are characterized by a defective DNA mismatch repair system, which generates highly immunogenic frame shift peptides (frameshift mutations, FSPs) that are not found on healthy tissue.

NOUS-209 is designed to comprise 209 shared FSP neoantigens, selected by Nouscom’s proprietary GENESIS (GE(netic)NE(oantigen)S(election)I(n)S(ilico)) algorithm, on the basis that an average of 50 neoantigens on any patient’s tumor will be shared with those in NOUS-209. Nouscom’s heterologous prime/boost platform clones these FSPs into Great Ape Adenoviral (GAd) and Modified Vaccinia Ankara (MVA) vectors, combined with other immunomodulators to harness the full power of the immune response, to generate the viral-vectored vaccine.

NOUS-209 is in Phase 1 clinical trial (NCT04041310), a multicenter, open label, multiple cohorts, first-in-human clinical study of NOUS-209 in combination with pembrolizumab, designed to evaluate safety, tolerability and immunogenicity and to detect preliminary evidence of anti-tumor activity.

On April 11, 2022 Adcendo ApS ("Adcendo"), a biotech company focused on the development of breakthrough antibody-drug conjugates (ADCs) for the treatment of underserved cancers, reported that a poster presentation will be provided on data of uPARAP targeting Antibody-Drug Conjugates in osteosarcoma preclinical xenograft models at the ongoing American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held in New Orleans from April 8-13, 2022 (Press release, ADCendo, APR 11, 2022, View Source [SID1234612020]).

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American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022

Presentation title: 2016 / 20 – Preclinical Evaluation of uPARAP (MRC2) Antibody-drug Conjugates (ADCE-003,010,011) in Osteosarcoma PDX Models
Session: Clinical Research Excluding Trials
Session Title: Paediatric Oncology: Clinical Investigation
Presenter: Yifei Wang
Authors: Yifei Wang, Wendong Zhang, Zhongting Zhang, Xiangjun Tian, Rossana N Lazcano Segura, Pooja Hingorani, Michael Roth, Jonathan Gill, Douglas Harrison, Zhaohui Xu, Jing Wang, Niels Behrendt, Christoffer F. Nielsen, Lars H. Engelholm, and Richard Gorlick
Date & Time: April 11th at 1:30 – 5.00 pm CDT

uPARAP is a cell-surface receptor, which is involved in collagen degradation and displays a differentiated expression profile between healthy tissue and cancer tissue, with several cancer types significantly overexpressing the receptor, including soft-tissue sarcoma, osteosarcoma, mesothelioma and glioblastoma multiforme (GBM). The preclinical study in Osteosarcoma PDX models presented at the 2022 AACR (Free AACR Whitepaper) meeting was carried out by researchers at the University of Texas MD Anderson Cancer Center.

Principal Investigator Richard Gorlick, M.D., Department Chair of the Department of Pediatrics Patient Care and Director of the Department of Pediatric Sarcoma Research Laboratory of The University of Texas MD Anderson Cancer Center, Houston, TX, said: "ADCs have shown robust clinical activity in several solid tumor cancers but, due to the lack of suitable targets, none are yet available for osteosarcoma. Osteosarcoma are the most common primary malignant bone tumors in children and young adults, where treatment has shown limited progress in the last few decades. We are encouraged by this data and look forward to further support the ongoing development of a uPARAP-targeting ADC in order to improve the outcome of our patients."

Niels Behrendt, Professor of the Finsen Laboratory, University of Copenhagen and Copenhagen University Hospital, and Scientific Co-founder of Adcendo, said: "After 25 years of research on the biology of uPARAP we are very encouraged by the promising activity data, suggesting that targeting uPARAP via ADCs could represent a novel therapeutic option for osteosarcoma patients and other underserved cancer indications."

On April 11, 2022 InventisBio Co., Ltd., a clinical-stage biotech company based in Shanghai, China reported that it has published the clinical data of their oral KRAS G12C inhibitor D-1553, for the first time in cancer patients (Press release, InventisBio, APR 11, 2022, View Source [SID1234612019]). These data are presented in two e-posters at the annual meeting of American Association of Cancer Research held on Apr 8-13 in New Orleans.

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KRAS G12C mutation is an oncogenic driver that occurs in approximately 15% of non-small cell lung cancer (NSCLC), 3% of colorectal cancer (CRC), and ~1% of several other solid tumors. D-1553 is a novel, potent and orally bioavailable KRAS G12C inhibitor developed by InventisBio. In a phase I international multi-center trial in patients with advanced or metastatic solid tumors harboring KRAS G12C mutation, D-1553 was evaluated in 22 patients and well tolerated without any dose limiting toxicity. Among 21 evaluable patients, a confirmed tumor objective response rate (ORR) of 19.0% was observed and a disease control rate (DCR) of 85.7% was achieved. Tumor response was seen at dose levels as low as 300 mg per day. In another study focusing on patients with NSCLC harboring KRAS G12C mutation, a group of 59 patients were included in the analysis and 52 of them were evaluable for tumor response. An ORR of 40.4% and a DCR of 90.4% were achieved, respectively. These are patients with advanced or metastatic cancers most of whom have been treated with two or more lines of systemic anticancer therapy.

"We are very excited to report our clinical data of D-1553 at the 2022 AACR (Free AACR Whitepaper) Annual Meeting. D-1553 is a key component of our clinical pipeline which covers therapeutic areas in cancer and metabolic disease. To our knowledge, this is the largest publicly reported population of patients that are treated with a KRAS G12C inhibitor developed completely in-house in China. We are committed to advancing this drug in more clinical studies to further assess its efficacy both as a single agent and in combination with other therapeutic agents in cancer patients and hope to make it available to them as a new treatment choice in the future," said Yaolin Wang, the CEO of InventisBio.

On April 11, 2022 PACT Pharma, Inc., a clinical-stage company developing transformational personalized neoantigen-specific T cell receptor (neoTCR) T cell therapies for the eradication of solid tumors, reported that new data highlighting several aspects of its first-of-its-kind personalized neoantigen platform for adoptive cell therapies were presented in five separate poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, PACT Pharma, APR 11, 2022, View Source [SID1234612018]). The breadth of presented data reflects the expansive collection of pioneering insights into patient-specific TCR repertoires against solid tumors that the company has been able to accumulate through analysis of research samples, as well as patient samples from its ongoing first-in-human Phase 1 trial. The AACR (Free AACR Whitepaper) conference is being held April 8-13, 2022, in New Orleans, Louisiana.

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"The scope of presented findings at AACR (Free AACR Whitepaper) highlights the significant progress that we have made across all aspects of our unique neoTCR T cell therapy platform, spanning identification and verification of patient-specific tumor driving mutations, gene editing, cell manufacturing, machine learning and bioinformatics," said Stefanie Mandl, Ph.D., senior vice president, head of research at PACT Pharma. "This continued progress speaks to the dynamic research and development approach that we are undertaking at PACT, as we aggressively advance our clinical-stage assets in human studies while using the evolving data set and learnings from our Phase 1 trial to continue to enhance various aspects of our technology platforms. This constellation of activities is focused on the single goal of bringing much needed, first-of-its kind neoTCR T cell therapies to patients battling solid tumors."

PACT is currently conducting a Phase 1 clinical trial evaluating the safety, tolerability and feasibility of adoptive cell therapy with its non-viral PACT^NV gene-edited autologous neoTCR T cells in advanced and metastatic solid tumors. This trial, in combination with extensive preclinical studies, has provided the company with unique data sets and insights derived from the core technologies that comprise its personalized adoptive T cell therapy platform for the treatment of solid tumors.

Key presented findings at AACR (Free AACR Whitepaper) included:

imPACT Isolation Technology Platform for TCR Discovery and Validation: Identifies TCRs to Patient-Specific Tumor Driver Mutations

By applying its imPACT Isolation Technology platform to peripheral blood samples of more than 170 patients with solid tumors, PACT generated key findings on the relative distribution of patient-private mutations versus mutations in known cancer driver genes. Data demonstrated that tumor-specific T cells preferentially recognize patient-private mutations. However, TCRs that target known cancer driver mutations were shown to constitute > 5% of the functionally characterized TCRs, highlighting a high-value opportunity for "off-the-shelf" TCR therapies. Based on these findings, PACT is expanding its platform to develop such "off-the-shelf" treatments, and anticipates filing an investigational new drug (IND) application in the second half of 2022.

Proprietary Machine Learning and Bioinformatics Optimize Personalized Treatment Strategies

In two separate AACR (Free AACR Whitepaper) posters, PACT highlighted its continued work building and utilizing its PACTImmune Database with extensive pre-, on- and post-treatment data from its ongoing Phase 1 trial. Analysis of this maturing data set with proprietary machine learning and bioinformatics produced new insights into patient-specific tumor immunogenicity in solid cancers, providing opportunities to optimize personalized neoTCR T cell treatment. The company’s application of its proprietary PACT-ESCAPE technology provided key learnings regarding neoepitope presentation escape mechanisms, which is a critical aspect of personalized TCR-based immunotherapy.

PACT^NV: Efficiently Enabling Single-Step Precision Gene Editing

In two separate poster presentations, PACT reported continued progress with PACT^NV, the company’s non-viral precision gene editing approach for generating clinical-grade TCR T cells for adoptive cell therapy. Importantly, the company has demonstrated the ability to execute precise, time-efficient, single-step gene editing to simultaneously knock-out TCR genes and insert neoantigen-specific TCRs isolated from a patient’s own blood. Furthermore, the company described its success incorporating additional complex modifications, which are intended to address challenges presented by the immunosuppressive nature of some tumor microenvironments, into the single-step gene editing process.

Copies of the posters presented at the AACR (Free AACR Whitepaper) conference are available on the "Events" page of the PACT Pharma website at: View Source

On April 11, 2022 Vivace Therapeutics, Inc., a small molecule discovery and development company developing first-in-class therapies targeting the Hippo pathway, reported that new preclinical data on the company’s transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor, VT3989, were reported at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Vivace Therapeurtics, APR 11, 2022, View Source [SID1234612016]). Presented findings demonstrated that the combination of VT3989 and osimertinib (Tagrisso), an epidermal growth factor receptor (EGFR) inhibitor, possessed enhanced anti-tumor activity and delayed tumor growth as compared to osimertinib alone in preclinical EGFR mutant tumor models. The AACR (Free AACR Whitepaper) conference is being held April 8-13, 2022, in New Orleans, Louisiana.

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Data reported in the poster presentation demonstrated that VT3989 exhibits strong synergistic activity with osimertinib. This was highlighted by the ability of the combination to enhance the blocking of tumor growth in EGFR mutant, non-small cell lung cancer (NSCLC) cell-line derived xenograft models, including the HCC827 model that is already known to be particularly sensitive to osimertinib. Furthermore, the combination of VT3989 and osimertinib significantly increased the life span of mice in an NCI-H1975 NSCLC CDX model as compared to osimertinib monotherapy.

Additionally, researchers showed similar synergistic activity in blocking tumor regrowth in human patient-derived xenograft models of EGFR mutant NSCLC. Of note, data demonstrated that TEAD inhibition achieved with VT3989 significantly delayed the re-emergence of tumor mass after osimertinib treatment resulted in non-palpable tumors. This finding offers evidence that EGFR mutant NSCLC relies upon dysfunction in the Hippo pathway to survive treatment with osimertinib, and can thus be targeted with TEAD inhibition.

"The exciting new data presented at AACR (Free AACR Whitepaper) not only support previous research highlighting the potency and selectivity of VT3989 as a TEAD inhibitor and its single agent anti-tumor activity in mesothelioma models, the findings also begin to build a compelling strategy around a synergistic combination treatment approach featuring VT3989 and EGFR inhibitors such as osimertinib," said Tracy Tang, Ph.D., vice president of biology at Vivace Therapeutics and lead author on the AACR (Free AACR Whitepaper) poster presentation. "We are eager to continue our pioneering research into the Hippo pathway and how addressing dysfunction in that pathway may pave the way for first-in-class cancer therapies capable of addressing the unmet needs of patients."

Vivace’s proprietary compounds inhibit palmitoylation of members of the TEAD protein family, including both covalent and non-covalent inhibitors. The company’s clinical candidate, VT3989, is currently in Phase 1 clinical trials. Pre-clinical research and development activities have demonstrated that the clinical candidate is active as a monotherapy against tumors that rely upon dysfunction of the Hippo pathway, and in combination with other anti-cancer therapies in additional tumor types.

The poster presented is available at the company’s website www.vivacetherapeutics.com.