On January 20, 2022 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that it will host a key opinion leader (KOL) webinar on hematological malignancies and prostate cancer on Tuesday, January 25, 2022 from 2:30 – 4:30 pm (ET) (Press release, Oncternal Therapeutics, JAN 20, 2022, View Source [SID1234605636]).

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The webinar will feature a presentation by KOL Michael Wang, M.D., from the MD Anderson Cancer Center, who will discuss the current landscape and unmet medical need in the treatment of Mantle Cell Lymphoma (MCL). Oncternal’s management will provide further details on the development of zilovertamab, the company’s investigational anti-ROR1 monoclonal antibody, including the planned registrational Phase 3 superiority study ZILO-301, which is expected to be initiated in the first half of 2022, following the company’s recently announced agreement with the U.S. Food and Drug Administration (FDA) regarding the study design and major details. Dr. Wang will serve as the U.S. Principal Investigator and Chairman of the Steering Committee for this study. Oncternal’s management will also discuss the progress in the development of ONCT-808, its lead candidate of its autologous CAR-T program targeting ROR1-expressing malignancies.

A second KOL, Evan Yu, M.D., from the Fred Hutchinson Cancer Research Center, will provide perspectives on current standards of care and highlight the potential of next generation treatments for patients with advanced prostate cancer. Oncternal’s management will present an overview of the preclinical data and development plans for ONCT-534, the lead candidate in its preclinical dual-action androgen receptor inhibitor (DAARI) program, a potential next-generation treatment option for patients with resistant prostate cancer.

A live question and answer session will follow the formal presentations. To register for the webinar, please click here.

Michael Wang, M.D. is Professor in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center. Dr. Wang has published more than 250 peer-reviewed papers and has presented his work at meetings nationally and internationally. He is the current Director of Mantle Cell Lymphoma (MCL) Program of Excellence and Co-Director of Clinical Trials at MD Anderson. During the past 22 years, he has focused on preclinical and clinical research and established a MCL-SCID-hu mouse model, which is the first human primary MCL animal model for the study of the biology and treatment of MCL. Dr. Wang has pioneered the work to improve the treatment of patients with MCL, including the introduction of BTK inhibitors such as ibrutinib and acalabrutinib in the treatment algorithm, and has performed extensive work with CAR-T cells for the treatment of these patients. His work has been published in the most prestigious medical journals, such as the New England Journal of Medicine and the Lancet. He is currently the PI of the B-Cell Lymphoma Moon Shot Program at MD Anderson. Dr. Wang obtained his M.D. from Shandong Medical University and M.S. from Beijing University, Medical School. He completed his clinical training as a resident at Norwalk Hospital, Norwalk, Conn., and as a Fellow in Oncology and in Hematology.

Evan Ya-Wen Yu, M.D., is a medical oncologist who treats prostate, bladder, and testicular cancer patients at Seattle Cancer Care Alliance (SCCA), Fred Hutch’s clinical care partner. In addition, Dr. Yu serves as the clinical research director of Genitourinary Medical Oncology at Seattle Cancer Care Alliance. Dr. Yu is also a professor of medical oncology at the University of Washington School of Medicine, a professor in clinical research at Fred Hutchinson Cancer Research Center, and medical director of clinical research support at Fred Hutchinson Cancer Research Consortium. As a physician-scientist, he provides a personalized-medicine approach to test novel therapies and discover unique cancer biomarkers. Dr. Yu also has a background in basic science; as a researcher, he studies the biological mechanisms of drug sensitivity and treatment resistance. In addition, his interests include cancer biomarkers, imaging (PET and MRI scans), and bone health. His overall goal is to discover novel biomarkers that can help guide treatment and aid in developing novel treatments for prostate cancer.

About Zilovertamab (formerly Cirmtuzumab)
Zilovertamab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Zilovertamab is currently being evaluated in a Phase 1b/2 clinical trial in combination with ibrutinib for the treatment of MCL or chronic lymphocytic leukemia (CLL), in a collaboration with the University of California San Diego (UC San Diego) School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, Oncternal is supporting two investigator-sponsored studies being conducted at the UC San Diego School of Medicine: (i) a Phase 1b clinical trial of zilovertamab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer, and (ii) a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory CLL.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen – not usually expressed on adult cells, and its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically targeting ROR1 expressing tumors. This led to the development of zilovertamab, that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when zilovertamab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. The FDA has granted Orphan Drug Designations to zilovertamab for the treatment of patients with MCL and CLL/small lymphocytic lymphoma. Zilovertamab is in clinical development and has not been approved by the FDA for any indication.

On January 20, 2022 Transgene (Euronext Paris: TNG), 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, jointly reported the publication of extensive preclinical proof-of-concept data for BT-001 in the Journal for ImmunoTherapy of Cancer (JITC) (Press release, Transgene, JAN 20, 2022, View Source [SID1234605652]). This peer-reviewed article demonstrates that their 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.

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Systemically administered anti-CTLA-4 antibodies, such as the approved ipilimumab, have demonstrated substantial efficacy but also clinically-limiting toxicity.

The JITC paper provides in vivo evidence 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 cells (Treg) depletion than ipilimumab.

"This strong preclinical data supports the development of our oncolytic virus BT-001 as an effective agent to treat solid tumors. We have vectorized a uniquely targeted anti-CTLA-4 antibody for intratumoral delivery and shown in vivo evidence that this reduces systemic toxicity, addresses ‘cold tumors’ and provides excellent tumor-selective Treg depletion. We are keenly anticipating progress in our ongoing Phase 1/2a clinical study with BT-001," said Bjorn Frendéus, Chief Scientific Officer of BioInvent.

"These data demonstrate the relevance of the approach which is based on combining our respective technologies to fully exploit the synergy between oncolytic vector, targeted delivery of a potent payload targeting immunosuppressive cells, and recruitment of effector T cells. The antitumor properties showed in this JITC publication give us great confidence in the results we expect from the further clinical development of BT-001," added Éric Quéméneur, Executive VP & Chief Scientific Officer of Transgene.

The safety-relevant data, published in JITC, show that a murine vector version of BT-001 delivered sustained levels of CTLA-4-receptor-saturating antibodies within tumors but low, sub-saturating exposure in blood and the non-tumor tissue. These antibody levels were associated with high depletion of Tregs in the tumor but the absence of systemic Treg depletion, notably in the spleen.

The study also provides 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 JITC paper is titled "Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject ‘cold’ tumors" and can be accessed here.

Recruitment in the ongoing Phase I/IIa clinical study of BT-001 (NCT04725331) in Europe 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.

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 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 January 20, 2022 -Pluristyx, Inc., an advanced therapy tools and services biotechnology company, panCELLa, a privately held biotechnology company, and Implant Therapeutics, a developer of genetically engineered stem cells, reported that they have entered into a manufacturing and distribution strategic alliance that offers cell therapy companies streamlined access to the next generation of safe, universal, cost-effective, "off-the-shelf" induced pluripotent stem cells (iPSCs) (Press release, Pluristyx, 20 20, 2022, View Source [SID1234605668]). The agreement will enable commercial access to iPSCs containing panCELLa’s FailSafe and Implant’s hypoimmunogenic technology derived from fully consented and regulatory appropriate donors. Both research and clinical grade panCELLa-owned iPSC lines will be manufactured and distributed by Pluristyx, who will also make custom iPSC lines incorporating panCELLa and Implant technology to meet unique customer needs.

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"We evaluated many manufacturing partners and concluded that Pluristyx’s proprietary platform and mRNA reprogramming technologies provided the ideal complement to our platform technologies. We think this combination of complementary skills will enable wide dissemination of our technology."

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Dr. Mahendra Rao, Chief Executive Officer of Implant, commented, "We evaluated many manufacturing partners and concluded that Pluristyx’s proprietary platform and mRNA reprogramming technologies provided the ideal complement to our platform technologies. We think this combination of complementary skills will enable wide dissemination of our technology."

"Pluristyx is excited to be working with panCELLa and Implant to commercialize their unique gene-edited platforms and iPSC lines. The combination of Pluristyx’s iPSC manufacturing and reprogramming technologies with panCELLa and Implant’s Stealth and FailSafe platforms will provide immediate access to a unique and ideal raw material for making the next generation of cell therapies," said Dr. Benjamin Fryer, Chief Executive Officer of Pluristyx.

On January 20, 2022 Champions Oncology, Inc. (Nasdaq: CSBR), a leading global technology-enabled biotech that is transforming drug discovery through innovative AI-driven pharmaco-pheno-multiomic integration, reported a therapeutic co-development partnership with Fannin Innovation Studio (Press release, Champions Oncology, JAN 20, 2022, View Source [SID1234605618]). The partnership will combine novel therapeutic targets identified within Champions’ Lumin platform with Fannin’s Therapeutic Raptamer platform to develop next generation Raptamer Drug Conjugates (RDC’s). RDCs engage tumor-specific therapeutic targets at a cell’s surface to deliver potent toxic payloads to the tumor, without affecting normal cells. The planned partnership will initiate with a single program focused on a previously unexplored target present in tumor indications such as non-small cell lung cancer (NSCLC), head and neck cancer, and other solid tumors. The partnership will also leverage the unique experimental platforms available at Champions to ensure rapid and efficient development towards clinical evaluation. Under the terms of this agreement, Champions and Fannin will share equal ownership of the developed therapeutic and establish a joint venture after specific development milestones are met.

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Ronnie Morris, MD, President and CEO of Champions Oncology, said "We’re excited to announce another partnership in drug discovery and development. Our experimental and digital research platforms continue to expand our understanding of tumor cell biology. With our AI-driven analytics, and deeply characterized dataset, we can completely reconstruct a tumor at the molecular level and identify differences between a tumor cell and normal cell. Over the past year, we have identified a considerable number of therapeutic targets that were previously overlooked using conventional methods, and we continue to scale our efforts to reveal others. The specific target being leveraged in this partnership has a profile that makes it uniquely interesting for an RDC-based therapeutic. Fannin’s Raptamer Platform is a compelling approach to therapeutic discovery, and we believe this partnership is the right approach for this target. We are eager to see this program develop with our combined expertise."

Atul Varadhachary, MD, PhD, Managing Partner of Fannin Innovation Studio, noted that "Our validated Raptamer platform provides a unique opportunity to rapidly develop selective, high-affinity ligands for targeted payload delivery to a variety of tissues, including tumors. The Raptamer platform provides complementary capabilities to Champions’ multiomic computational platform, and we are excited about our joint venture with Champions as well as the initial neo-antigenic target for our partnership."

On January 20, 2022 Vigeo Therapeutics, a clinical-stage immuno-oncology company pioneering novel cancer therapies, reported its lead candidate VT1021 will advance into a Phase 2-3 registrational study through the company’s collaboration with the Global Coalition for Adaptive Research (GCAR) (Press release, Vigeo Therapeutics, JAN 20, 2022, View Source [SID1234605637]). VT1021 will be part of GCAR’s GBM AGILE Phase 2-3 adaptive platform trial for patients with glioblastoma.

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VT1021 is a first-in-class compound that, by binding to MDSCs, induces the expression of thrombospondin-1 (Tsp-1) in the tumor microenvironment (TME). Tsp-1 then blocks the CD47 immune checkpoint and reprograms the CD36 receptor to induce tumor cell apoptosis, inhibit angiogenesis, and reprogram macrophages from the M2 to M1 phenotype.

GBM AGILE is a patient-centered adaptive platform trial to support registration that tests multiple therapies for patients with newly diagnosed and recurrent glioblastoma (rGBM) – the deadliest form of brain cancer.

VT1021 was selected for inclusion in the global AGILE Phase 2-3 trial based on the unique and relevant mechanism of action and the existing strong preliminary clinical data from the completed open-label, multicenter Phase 1/2 study (NCT03364400), evaluating the safety and preliminary anti-tumor efficacy of single-agent VT1021 in subjects enrolled in both dose escalation and dose expansion cohorts.

In the rGBM expansion cohort, VT1021 demonstrated significant single agent activity. Among 22 evaluable GBM subjects, 3 had complete response (CR), 1 had partial response (PR), and 7 had stable disease (SD). The overall disease control rate (DCR) was 50%. In the responder group, the average time on study was over 300 days with 2 subjects on study for over 480 days at the conclusion of the study. These two subjects continued to receive VT1021 through an extension study and have both have gone over 525 days receiving VT1021.

"We are excited that GCAR selected VT1021 for its Phase 2-3 study for patients with glioblastoma," said Vigeo COO Dr. Jing Watnick. "In the expansion study, VT1021 demonstrated noteworthy single-agent clinical activity in rGBM, particularly in subjects with high expression levels of CD36 and CD47, and we believe it could be an important new treatment option for patients. We look forward to providing an update when the trial commences."

Vigeo also plans to initiate efficacy studies in additional solid tumor indications, including pancreatic cancer, with its lead candidate, VT1021 during the first half of 2022.

About VT1021
Vigeo’s lead asset, VT1021, is a first-in-class dual modulating compound that blocks the CD47 immune checkpoint and activates CD36, which induces apoptosis and increases the M1:M2 macrophage ratio. VT1021 achieves this through stimulation of thrombospondin-1 (Tsp-1). The goal of these dual-modulating effects is conversion of immuno-suppressive, or "cold," tumors that don’t respond to immuno-oncology agents, to immuno-stimulated, or "hot," tumors that are potentially more receptive to immuno-oncology agents. Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors.