On June 10, 2022 Step Pharma, a world leader in CTPS1 inhibition for the targeted treatment of cancer, reported that it is presenting encouraging data in three posters for its first-in-class, highly selective, orally bioavailable CTPS1 inhibitor STP938 at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress being held June 9-17, 2022 in Vienna, Austria (Press release, Step Pharma, JUN 10, 2022, View Source [SID1234615879]).

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The data presented demonstrate the high specificity of CTPS1 inhibition achieved with STP938, with inhibition of human neoplastic T cell growth shown both in vivo and in vitro. Moreover, inhibition of CTPS1 by STP938 shows anti-proliferative activity in multiple myeloma through the induction of replication stress and demonstrates synergistic activity when combined with ATR inhibition.

These data support Step Pharma’s belief in STP938’s targeted cytotoxic potential in haematological cancers. STP938 displays favourable preclinical safety and pharmacological properties and is due to progress into first in human clinical studies in the second half of 2022.

Philip Beer, Head of Research and Translational Medicine at Step Pharma, commented: "Our promising findings demonstrate the importance of CTPS1 for cancer cell proliferation and the potential of STP938 as a targeted therapy for the treatment of cancers with high unmet clinical need. CTPS1 plays a crucial role in neoplastic cells, where inhibiting its activity could have a significant impact in a number of different cancers, either as monotherapy or in combination with existing or novel cancer drugs. We look forward to progressing this exciting new therapy into the clinic."

Andrew Parker, Chief Executive Officer of Step Pharma, said: "Our deep understanding of the pathways and CTPS1 biology has led to the development of STP938, a targeted therapy with predicted superior safety and efficacy profiles compared to existing treatments. We believe that this highly selective treatment has the potential to kill cancer cells without affecting immune cell differentiation and therefore could represent a significant step change in the way we treat cancer."

Full details of the posters are:

Poster Presentation: CTP synthase 1 (CTPS1) is a novel target in T cell cancers, with small molecule inhibition inducing death of neoplastic human T cells in vitro and inhibition of their growth in an in vivo xenotransplant model

Authors: Philip Beer, Hélène Asnagli, Norbert Minet, Eef Hoeben, Andrew Parker, Alain Fischer, Sylvain Latour

Date and Time: Available from June 10, 09:00 CEST and on-demand until Monday, August 15, 2022, on the Congress platform

Session title: Lymphoma Biology & Translational Research

Poster presentation: CTPS1 is a novel therapeutic target in myeloma – selective small molecule inhibition delivers single agent activity and synergises with ATR inhibition

Authors: Christina Pfeiffer, Philip Beer, Hélène Asnagli, Arnold Bolomsky, Alexander Grandits, Anja Schneller, Julia Huber, Niklas Zojer, Martin Schreder, Andrew Parker, Heinz Ludwig

Date and Time: Available from June 10, 09:00 CEST and on-demand until Monday, August 15, 2022, on the Congress platform

Session title: Myeloma and other monoclonal gammopathies – Biology & Translational Research

Poster Presentation: Selective small molecule inhibition of CTP synthase 1 (CTPS1) suppresses T cell proliferation and cytokine release, highlighting a novel therapeutic target for graft-versus-host disease

Authors: Philip Beer, Andrew Parker, Hélène Asnagli

Date and Time: Available from June 10, 09:00 CEST and on-demand until Monday, August 15, 2022, on the Congress platform

Session title: Stem cell transplantation – Experimental

On June 10, 2022 The SHINE Technologies reported that gearing up for this year’s SNMMI Annual Meeting, June 11-14 in Vancouver, British Columbia (Press release, Shine Medical Technologies, JUN 10, 2022, View Source [SID1234615878]). Leading molecular-imaging and nuclear-medicine professionals from every corner of the industry will come together to share in-depth views of the latest research and development, as well as share insights into practical clinical applications.

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After two years of holding virtual events, we’re excited to attend SNMMI’s first in-person conference since 2019. This year’s theme is "Advancing Precision Imaging and Therapy."

We’ll be sharing progress on our diagnostics and therapeutics divisions during exhibit hours. Our proprietary isotope production processes create molybdenum-99 and non-carrier-added lutetium-177 used in tens of thousands of daily procedures to diagnose and treat heart disease and late-stage cancer. Our contribution to these markets will increase access to life-saving capabilities, including improving industrial equipment safety and diagnosing and treating cancer, heart disease, and other illnesses.

We are already producing lutetium-177 on a small scale for preclinical and clinical trials, and our process was validated for Good Manufacturing Practice earlier this year. We plan to continue to scale production of Lu-177 on the way to our large-scale production facility going online in 2024.

Our large-scale molybdenum-99 production facility is expected to be the largest facility in the world dedicated solely to producing medical isotopes. It is slated to go online late next year.

Chris Vessell, SHINE’s new General Manager of the Therapeutics Division, will be in attendance.

"I am excited to bring my experience to such a talented, visionary team at SHINE," said Vessell. "Their technology and vision for the future will be a game-changer as the company continues to pioneer new methods of nuclear medicine and delivers cancer therapies that make immeasurable differences for patients and their families."

If you want to say "hi" to Chris, or learn how SHINE Technologies is working to help improve medical outcomes through fusion technology, stop by and see us at Booth No. 36 at the show. If you have any questions in advance, send us a note at [email protected] or visit our virtual booth.

On June 10, 2022 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that preclinical data from its ROR1-targeting cell therapy programs will be highlighted in a poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress (Press release, Oncternal Therapeutics, JUN 10, 2022, View Source [SID1234615875]). Oncternal’s collaborators from the Karolinska Institutet in Stockholm, Sweden, have conducted a series of preclinical studies evaluating T cells as well as Natural Killer cells expressing Oncternal’s ROR1 CAR containing the antigen binding region of zilovertamab. The ROR1 CAR mediated target recognition and cell activation when expressed in either T cells or NK cells. Also, ROR1 CAR-T cells demonstrated dose-dependent anti-tumor activity in a mantle cell lymphoma mouse model.

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Poster Title: Preclinical Evaluation of Zilovertamab-Based Anti-ROR1 Chimeric Antigen Receptors in NK and T Cells
Abstract Number: P1435
Session Title: Gene therapy, cellular immunotherapy and vaccination – Biology & Translational Research
Session Date and Time: June 11, 2022 from 9:00am CEST
"Despite recent significant advances in treating hematological malignancies with current CAR-based cell therapies, certain limitations remain, such as treatment failures due to tumor antigen escape, and toxicities including induction of immunodeficiencies like B-cell aplasia. Patients are in need of more effective treatment options" said Evren Alici, M.D., Ph.D., Associate Professor and group leader of the Cell and Gene Therapy Group, HERM, Department of Medicine, Karolinska Institutet. "The ROR1-targeting cell therapies have shown strong activity in our lymphoma models. We are now working with our Oncternal colleagues to evaluate the therapies in models of other tumor indications. With our strong focus on NK cells, we are excited to further study ROR1 CAR-NK cells within our NextGenNK competence center."

"Based on the wide expression of ROR1 across tumor indications and its underlying importance in cancer biology as well as the safety and efficacy shown by zilovertamab in our clinical studies, we believe that targeting ROR1 using zilovertamab-based CAR cell therapy might offer a potentially effective treatment option for patients suffering from unmet medical needs, including heme malignancies and solid tumors" said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "In preclinical research, our zilovertamab-derived ROR1 cell therapies have demonstrated anti-tumor activity in a series of studies, including these presented here by our colleagues from the Karolinska Institutet. We are working closely with Professor Evren Alici and his team to evaluate our ROR1 cell therapies using T cells and NK cells, thus potentially laying the foundation for an off-the-shelf cell therapy program. Oncternal is proud to be an industry partner of the NextGenNK competence center located at the Karolinska Institutet. Near-term, we are looking forward to dosing the first patient with our autologous ROR1 CAR-T cell therapy, ONCT-808, in the coming months."

ONCT-808 is the Company’s lead autologous ROR1-targeted CAR-T cell therapy program candidate. The program is advancing towards an Investigational New Drug (IND) application submission expected in mid-2022.

On June 10, 2022 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that the rationale and plans for its upcoming Phase 3 ZILO-301 (zilovertamab plus ibrutinib targeting ROR1 for patients with Mantle Cell Lymphoma) clinical trial will be highlighted in a poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress (Press release, Oncternal Therapeutics, JUN 10, 2022, View Source [SID1234615874]). ZILO-301 is designed to evaluate the efficacy and safety of zilovertamab, an investigational anti-ROR1 monoclonal antibody, plus ibrutinib compared to ibrutinib monotherapy for the treatment of patients with relapsed or refractory mantle cell lymphoma (R/R MCL).

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Poster Title: Study ZILO-301: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Zilovertamab Plus Ibrutinib vs. Ibrutinib in Patients with Relapsed or Refractory Mantle Cell Lymphoma
Abstract Number: P1154
Session Title: Indolent and mantle-cell non-Hodgkin lymphoma – Clinical
Session Date and Time: June 10, 2022 at 16:30 CEST
"The recently announced updated interim data from our Phase 1/2 study presented at ASCO (Free ASCO Whitepaper) 2022, provides ample support for the rationale of the design of our global registration Phase 3 study, ZILO-301, evaluating the combination of zilovertamab and ibrutinib in patients with MCL," noted Salim Yazji, M.D., Oncternal’s Chief Medical Officer. "We are excited to pursue a registrational pathway for zilovertamab based on an innovative enrichment study design that we believe can provide both an accelerated approval and regular approval in a single study. We expect to initiate ZILO-301 in the third quarter of 2022."

Zilovertamab is being evaluated in combination with ibrutinib in patients with R/R MCL and chronic lymphocytic leukemia (CLL) in the Phase 1/2 study, CIRM-0001. The most recent interim data update showed an Objective Response Rate (ORR) of 85% and a Complete Response (CR) rate of 41% in 27 evaluable patients with mantle cell lymphoma, both of which compare favorably to the historical ORR of 66% and CR rate of 20% for ibrutinib monotherapy.

The phase 3 study, ZILO-301, will evaluate the potential benefit for patients who achieve either a partial response (PR) or stable disease (SD) during a lead-in with ibrutinib monotherapy. Initially, patients enrolled in ZILO-301 will receive single agent ibrutinib (560 mg daily) for 4 months. Patients with an inadequate response (PR or SD) will be randomized (1:1) to receive zilovertamab or placebo while continuing to receive ibrutinib. The study aims to randomize approximately 250 patients.

Key Inclusion criteria:
Adults with histologically confirmed MCL
Relapsed or refractory with at least 1 prior therapy
Primary Objective
Progression-free survival (PFS) among subjects who had a PR or SD after open-label ibrutinib monotherapy phase and were randomized to receive zilovertamab + ibrutinib or ibrutinib + placebo
Secondary Objectives
Objective Response Rate (ORR) and Duration of Response (DoR)
Complete Response Rate (CR Rate)
Overall Survival (OS)
Proportion of subjects experiencing grade 3 or 4 neutrophil count decrease and overall safety profile
About Zilovertamab

Zilovertamab is an investigational, humanized, potentially first-in-class monoclonal antibody targeting Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1). Zilovertamab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of patients with MCL, chronic lymphocytic leukemia (CLL) or MZL, 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, a Phase 1b clinical trial for patients with metastatic castration-resistant prostate cancer (mCRPC), and a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, for patients with relapsed/refractory CLL. Both are open for enrollment.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen, not usually expressed on adult cells, but 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 inhibiting ROR1-expressing tumors. This led to the development of zilovertamab which binds this critical epitope of ROR1, 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 June 10, 2022 NuCana plc (NASDAQ: NCNA) reported that data to be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress highlighting the activity of NUC-7738, a phosphoramidate transformation of 3’-deoxyadenosine (3’-dA), in a broad range of Acute Myeloid Leukemia (AML) cell lines. NUC-7738 has already shown promise as monotherapy in patients with solid tumors in a Phase 1/2 study (NuTide:701) and will also be combined with a PD-1 checkpoint inhibitor (Press release, Nucana BioPharmaceuticals, JUN 10, 2022, View Source [SID1234615873]).

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The data at EHA (Free EHA Whitepaper) 2022 show that NUC-7738 can suppress the expansion and survival of AML cells by reducing β-catenin signaling, a key pathway in AML. NUC-7738’s effect was observed in multiple different AML cell lines suggesting broad therapeutic potential. Furthermore, it was observed that NUC-7738 resulted in a reduction of the cells that are resistant to standard chemotherapy drugs and thought to be responsible for disease relapse.

These findings, combined with the anti-cancer activity and favorable safety profile of NUC-7738 observed in the NuTide:701 study provide a strong rationale for the evaluation of NUC-7738 in patients with leukemia.

The details of NuCana’s poster presentation at EHA (Free EHA Whitepaper) are as follows:

Title: NUC-7738 regulates β-catenin signaling resulting in reduced proliferation and self-renewal of AML cells
Abstract Number: P459
Presentation Date & Time: Friday June 10, 2022 from 16:30-17:45 CEST (e-poster online at 9:00 CEST)
Presenting Author: Akbar M. Shahid

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "NUC-7738 has entered Phase 2 development in patients with solid tumors and we have been encouraged by the clinical activity and favorable safety profile we have observed. The data presented at EHA (Free EHA Whitepaper) indicate that NUC-7738 may have applications beyond solid tumors and we are currently evaluating the optimal pathway for NUC-7738’s development for the treatment of hematologic malignancies."

About NUC-7738
NUC-7738 is a ProTide transformation of 3′-deoxyadenosine (3′-dA), also known as cordycepin. 3’-dA has demonstrated potent anti-cancer activity in non-clinical studies, but has not been successfully developed as an anti-cancer agent due to its rapid breakdown by adenosine deaminase (ADA). NUC-7738 is designed to generate the active anti-cancer metabolite of 3’-dA directly inside cancer cells, thus overcoming 3’-dA’s key limitations of breakdown, transportation and activation. The cytotoxic effect of NUC-7738 is largely attributed to the generation of the main active anti-cancer metabolite, 3′-dATP. Primarily, 3′-dATP interferes with RNA polyadenylation, causing changes in the expression of genes involved in metabolism, differentiation, and apoptosis, ultimately leading to metabolic stress, cessation of cancer-cell growth and cell death.