On March 9, 2022 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of small protein therapeutics to address difficult-to-treat cancers, reported that two abstracts have been accepted for presentation during the late-breaking research sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 8-13, 2022 in New Orleans, LA (Press release, Sapience Therapeutics, MAR 9, 2022, View Source [SID1234609808]).

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Details of the poster presentations are as follows:

Abstract Number: 8125
Title: Characterizing the PK/PD relationship of C/EBPβ antagonist peptide ST101 in a mouse orthotopic breast cancer model
Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 2
Session Date and Time: 4/13/2022 9:00:00 AM
Location: New Orleans Convention Center, Poster Section 16

Abstract Number: 8148
Title: β-catenin antagonist peptide, ST316, attenuates Wnt-dependent oncogenic activity
Session Title: Late-Breaking Research: Molecular/Cellular Biology and Genetics 1
Session Date and Time: 4/11/2022 9:00:00 AM
Location: New Orleans Convention Center, Poster Section 16

Abstracts and full session details can be accessed through the AACR (Free AACR Whitepaper) meeting planner: AACR (Free AACR Whitepaper) Annual Meeting 2022 | April 8-13, 2022 | New Orleans

About ST101
ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). This is an open-label, two-part, Phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 in patients with advanced solid tumors. The study consists of two phases: a Phase 1 dose escalation/regimen exploration phase and a Phase 2 expansion phase. In the ongoing dose escalation study, ST101 has demonstrated clinical proof-of-concept with a RECIST 1.1-confirmed partial response (PR) in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. In the ongoing Phase 2 dose expansion part of the study, Sapience has initiated dosing in patients with GBM and metastatic cutaneous melanoma, and will soon commence dosing in patients with refractory, locally advanced or metastatic hormone-receptor-positive breast cancer and castrate-resistant prostate cancer. ST101 has been granted Fast Track designation for recurrent GBM and advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, as well as Orphan designation from the U.S. Food and Drug Administration and the European Commission for the treatment of glioma.

About ST316
ST316, a first-in-class β-catenin antagonist, is currently being evaluated in IND-enabling studies. β-catenin is a critical member of the canonical Wnt signaling pathway, a well-known development stage pathway that has been considered an "undruggable" cancer target, as small molecules have proven ineffective or toxic. Wnt/β-catenin signaling drives cancer initiation and contributes to tumor growth, angiogenesis and metastasis. ST316 exerts its activity through disruption of the BCL9/β-Catenin interaction to suppress transcription of Wnt target genes regulating proliferation, migration, invasion, and the metastatic potential of tumor cells.

On March 9, 2022 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported that management will be presenting at the virtual 32nd Annual Oppenheimer Healthcare Conference and participating in the Targeted Oncology Panel as part of the Conference (Press release, Cyclacel, MAR 9, 2022, View Source [SID1234609807]).

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Conference details can be found below:

Panel: Targeted Oncology 2.0 – Moving Beyond TKIs
Date: March 14th, 2022
Time: 10:00am ET
Format: Fireside Chat (Registration Link)

Company Presentation
Date: March 17th, 2022
Time: 12:40pm – 1:10pm ET
Format: Fireside Chat (Registration Link)
A replay will be available following the presentation for 90 days

On March 9, 2022 Transgene a biotech company that designs and develops virus-based immunotherapeutics against cancer, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported that an abstract reporting preclinical studies of BT-001, a novel oncolytic virus, has been selected for a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Transgene, MAR 9, 2022, View Source [SID1234609806]). The conference will be held in person in New Orleans, LA, April 8-13, 2022.

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The poster will highlight that BT-001, a co-developed clinical stage product, based on Transgene’s patented oncolytic vector and encoding BioInvent’s proprietary anti-CTLA-4 antibody, has the potential to provide greater therapeutic benefit than systemically administered anti-CTLA-4 antibodies.

The preclinical data to be presented demonstrate that vectorized anti-CTLA-4 antibodies delivered intratumorally (i.t.) can improve safety by reducing their systemic exposure. Efficacy may also be improved, with evidence from the immunocompetent murine model showing that vectorized anti-CTLA-4 antibodies have anti-tumoral activity even against ‘cold tumors’ that are resistant to systemically-delivered checkpoint inhibitors.

Furthermore, the precise targeting of the antibody to a unique functional epitope of CTLA-4 provides a higher level of regulatory T cell (Treg) depletion than currently available immune checkpoint blockade (ICB) therapies.

The studies also provide several key insights into likely mechanisms underlying the efficacy of BT-001. Vectorized anti-CTLA-4:

· triggered both Fcγ-receptor-dependent Treg depletion and antigen cross-presentation – mechanisms known to trigger and promote long-lasting, systemic, CD8+ T cell antitumor immunity;
· showed broad antitumor activity, including activity against murine ‘cold tumor’ models which are resistant to systemic checkpoint inhibitors;
· showed additive or synergistic anti-tumor activity when combined with anti-PD-1.

The details of the poster presentation are as follows:

Abstract Title: Comprehensive preclinical studies of BT-001: an oncolytic vaccinia virus armed with Treg-depleting @CTLA4 and GM-CSF.

Authors: Jean-Baptiste Marchand, Monika Semmrich, Christelle Remy, Matilda Rehn, Laetitia Fend, Petra Holmkvist, Nathalie Silvestre, Carolin Svensson, Patricia Kleinpeter, Jules Deforges, Fred Junghus, Linda Mårtensson, Johann Foloppe, Ingrid Teige, Björn Frendéus, Éric Quéméneur.

Session Category: Immunology

Session Title: Vaccines: Oncolytic and Prophylactic

Session Date and Time: Tuesday Apr 12, 2022, 1:30 PM – 5:00 PM

Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 40

Poster Board Number: 17

Abstract Number: 3567

The abstract can be accessed on the AACR (Free AACR Whitepaper) annual meeting website: View Source

About BT-001

BT-001 is an oncolytic virus generated using Transgene’s Invir.IO platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response. As a consequence, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody will be greatly improved.

BT-001 is currently in a Phase I/IIa clinical study (NCT04725331) and recruitment is progressing steadily. The trial assesses BT-001 as a single agent and in combination with the PD-1 checkpoint inhibitor pembrolizumab against solid tumors. Initial Phase I data are expected in the first half of 2022.

BT-001 is being co-developed as part of a 50/50 collaboration on oncolytic viruses between Transgene and BioInvent. To know more on BT-001, watch our video here.

On March 9, 2022 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer reported that it will be presenting a poster with new and promising preliminary Phase I data on TG4050, its individualized neoantigen cancer vaccine, at the AACR (Free AACR Whitepaper) (American Association for Cancer Research) Annual Meeting 2022 (Press release, Transgene, MAR 9, 2022, View Source [SID1234609805]). AACR (Free AACR Whitepaper) will take place in New Orleans, Louisiana, USA, April 8 – 13.

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The abstract has been accepted for a late-breaking session and will be made available on the AACR (Free AACR Whitepaper) Online Itinerary Planner and Meeting App on April 8, 2022.

TG4050 is the first candidate based on Transgene’s myvac platform. Powered by NEC’s cutting-edge AI capabilities, TG4050 is being evaluated in two ongoing multicenter Phase I trials in patients with ovarian cancer and head and neck cancer

Poster title: Phase I trials of personalized cancer vaccine TG4050 in surgically treated high-risk head and neck squamous cell carcinoma (HNSCC) and relapsing ovarian cancer (OvC) patients • Session title: Phase I Clinical Trials 2 • Poster and abstract number: CT182 • Date, time, location: Tuesday Apr 12, 2022 9:00 AM-12:30 PM CDT, Board 7, Section 33 • Authors: M. Block, JP Delord, C. Ottensmeier, C. Le Tourneau, A. Lalanne, O. Lantz, K. Knutson, G. Lacoste, A. Tavernaro, M. Brandely, N. Silvestre, B. Grellier, Y. Yamashita, O. Kousuke, N. Yamagata, E. Quemeneur, K. Bendjama

About the clinical trials
TG4050 is being evaluated in two Phase I clinical trials for patients with ovarian cancer (NCT03839524) and HPV-negative head and neck cancers (NCT04183166). In a first Phase I trial, TG4050 is being administered to patients with HPV-negative head and neck cancer. A personalized treatment is created for each patient after they complete surgery and while they receive an adjuvant therapy. Half of the participants receive their vaccine immediately after they complete their adjuvant treatment. The other half is given TG4050 as an additional treatment at the time of recurrence of the disease. This randomized study is evaluating the treatment benefits of TG4050 in patients who have a high risk of relapse. Up to 30 patients will receive TG4050 in France, in the UK and in the USA. The principal investigator of the trial is Prof. Christian Ottensmeier, MD, PhD, Consultant Medical Oncologist at the Clatterbridge Cancer Centre and Professor of Immuno-Oncology at the University of Liverpool. In France, the clinical trial is being conducted, at Institut Curie, Paris, by Prof. Christophe Le Tourneau, MD, PhD, Head of the Department of Drug Development and Innovation (D3i) and at the IUCT-Oncopole, Toulouse, by Prof. Jean-Pierre Delord. In the USA, the trial is being led by Dr. Yujie Zhao, MD, PhD, at the Mayo Clinic. Endpoints of the trial include safety, feasibility and biological activity of the therapeutic vaccine. In parallel, a Phase I clinical trial of TG4050 is enrolling patients with ovarian cancer.

The first patient has been dosed in the USA. This second trial is including patients after surgery and first-line chemotherapy. Dr. Matthew Block, MD, PhD, Consultant Medical Oncology, Consultant Immunology and Associate Professor of Oncology at the Mayo Clinic (USA) is the principal investigator of the trial; in France, the trial is being conducted by Prof. Le Tourneau, MD, PhD, at Institut Curie and by Dr. Alexandra Martinez, MD, Associate Head of Surgical Department, at IUCT-Oncopole. Endpoints of the trial include safety, feasibility and biological activity of the therapeutic vaccine. First positive preliminary data on these two Phase I trials have been communicated in November 2021. More information can be found here, or in a short video here. About myvac myvac is a viral vector (MVA – Modified Vaccinia Ankara) based, individualized immunotherapy platform that has been developed by Transgene to target solid tumors. myvac-derived products are designed to stimulate the patient’s immune system, recognize and destroy tumors using the patient’s own cancer specific genetic mutations. Transgene has set up an innovative network that combines bioengineering, digital transformation, established vectorization knowhow and unique manufacturing capabilities.

Transgene has been awarded "Investment for the Future" funding from Bpifrance for the development of its platform myvac. TG4050 is the first myvac-derived product being evaluated in clinical trials. Click here to watch a short video on myvac. About TG4050 TG4050 is an individualized immunotherapy being developed for solid tumors that is based on Transgene’s myvac technology and powered by NEC’s longstanding artificial intelligence (AI) expertise. This virus-based therapeutic vaccine encodes neoantigens (patient-specific mutations) identified and selected by NEC’s Neoantigen Prediction System.

The prediction system is based on more than two decades of expertise in AI and has been trained on proprietary data allowing it to accurately prioritize and select the most immunogenic sequences. TG4050 is designed to stimulate the immune system of patients in order to induce a T-cell response that is able to recognize and destroy tumor cells based on their own neoantigens. This individualized immunotherapy is developed and produced for each patient

On March 9, 2022 Orion’s collaboration Bayer reported the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) as well as the submission of a Variation Type II to the European Medicines Agency (EMA) for the oral androgen receptor inhibitor (ARi) darolutamide. Bayer is seeking approval for the use of darolutamide in combination with docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC) (Press release, Bayer, MAR 9, 2022, View Source [SID1234609804]). The compound is already approved in more than 60 markets around the world, including the U.S., the European Union (EU), Japan and China, under the brand name Nubeqa, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease.

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The submissions are supported by positive results from the Phase III ARASENS trial, showing a statistically significant improvement in overall survival (OS) for darolutamide plus ADT and docetaxel in men with mHSPC. These results were presented in February at the 2022 ASCO (Free ASCO Whitepaper) GU Cancers Symposium and simultaneously published in The New England Journal of Medicine.

Darolutamide is developed jointly by Orion and Bayer. Additional filings in mHSPC are planned by Bayer globally. The compound is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE) as well as an ANZUP-led international co-operative group Phase III trial, evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP, ANZUP1801).

About the ARASENS Trial

The ARASENS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the efficacy and safety of oral darolutamide, an androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, plus ADT and docetaxel.

The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all measured at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability.

About Metastatic Hormone-Sensitive Prostate Cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.1

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 5% of men will already suffer from prostate cancer with distant metastases when first diagnosed. Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of the chemotherapy docetaxel and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.

About darolutamide

Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. A low blood-brain barrier penetration would explain the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial and the improved verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.

The product is approved under the brand name Nubeqa in more than 60 markets around the world, including the U.S., EU, Japan, China, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. The compound is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE) as well as an ANZUP-led international co-operative group Phase III trial, evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP, ANZUP1801). Information about these trials can be found at www.clinicaltrials.gov.