On December 10, 2023 Remedy Plan Therapeutics ("Remedy Plan"), a small molecule therapeutics start-up company transforming the field of NAMPT inhibition, reported new data to be shared during an oral presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego, California, December 9-12th (Press release, Remedy Plan, DEC 10, 2023, View Source [SID1234638387]).

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Remedy Plan will present data on RPT1G, a clinical drug candidate for the treatment of solid and hematological malignancies. RPT1G is a small molecule NAMPT inhibitor with a unique, first-in-class mechanism of action that is optimized to preserve the cellular metabolism in healthy cells, while inhibiting activity in malignant cells. This is achieved through hyperbolic inhibition of NAMPT that is fractional and highly tunable. Preclinical and animal studies revealed that RPT1G is efficacious in acute leukemia, lymphoma, and solid tumor models, selectively killing cancer cells. Importantly, RPT1G was thousands-fold better tolerated by healthy cells, without the severe on-target toxicities reported for other NAMPT inhibitors.

"We are excited to introduce our clinical candidate RPT1G, a first-in-class NAMPT drug that shows efficacy without the severe on-target toxicities seen with other NAMPT inhibitors," said Greg Crimmins, Ph.D., CEO and Founder of Remedy Plan. "NAMPT dysregulation is responsible for more than 20 diseases, but efforts to target NAMPT to date have been hampered by on-target toxicities. Our groundbreaking mechanism of action has the potential to revolutionize the field of NAMPT inhibition, unlocking opportunities for treating hematological malignancies and solid tumors, as well as autoimmune and metabolic diseases."

NAMPT is central to cancer metabolism and is up-regulated in many solid and hematological malignancies, making it a high-value oncology target. Based on the promising data presented at ASH (Free ASH Whitepaper), RPT1G will be advancing to the clinic in 2024.

Abstract and Presentation details:

Remedy Plan’s CEO and Founder Greg Crimmins, Ph.D. will present the data on Sunday December 10th at 10:30AM PST in Grand Hall B of the Manchester Grand Hyatt San Diego, and all meeting participants are encouraged to attend either in person or online.

A 1st-in-Class Small Molecule NAMPT Inhibitor as a Novel Therapeutic for Acute Lymphocytic Leukemia. Abstract #419, Oral Session: 605, Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Targeted Therapy in Lymphoid Leukemias. The full abstract is available here.

On December 10, 2023 Taiho Oncology, Inc. reported results of a U.S. real-world study of oral decitabine and cedazuridine (DEC-C) in patients with myelodysplastic syndromes (MDS), a rare form of blood cancer (Press release, Taiho, DEC 10, 2023, View Source [SID1234638386]). Results of the retrospective real-world analysis of use patterns for hypomethylating agents suggest oral DEC-C as a treatment option with the potential to reduce patient and caregiver burden, while maintaining patients on therapy. Data from the study were shared during an oral presentation (Abstract #548) at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition.

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"For patients with myelodysplastic syndromes, therapy with intravenous or subcutaneous hypomethylating agents has been associated with increased patient burden, which can adversely affect treatment compliance and, subsequently, outcomes," said Amer Zeidan, MBBS, MHS, Associate Professor of Medicine (Hematology), Yale School of Medicine, Interim Chief, Hematologic Malignancies, Yale Cancer Center and Smilow Cancer Hospital, and study investigator. "Previous studies have shown that oral decitabine and cedazuridine provides comparable safety and efficacy to parenteral HMAs,1,2,3 and what we found in this real-world study is that this oral therapy resulted in a trend for improved persistence as treatment extended beyond the first six months. Based on these results and the potential for reduced treatment burden, oral decitabine and cedazuridine may be a viable alternative to intravenous or subcutaneous HMAs."

In this study of 1,569 patients, 160 received oral DEC-C and 1,409 received intravenous/subcutaneous (IV/SC) HMAs. After matching, there were 158 patients in each treatment cohort. Longitudinal persistence – the accumulation of time from initiation to discontinuation of therapy4 – was comparable between the matched oral DEC-C and intravenous/subcutaneous HMA cohorts during the first 6 months post-index, with similar proportions receiving the maximum number of treatment cycles (based on a 28-day cycle) at each month following index (73.8% vs 71.1%, 46.5% vs 48.7% and 28.6% vs 24.8%, for 2, 4 and 6 months, respectively). However, a trend toward improved persistence with oral DEC-C versus intravenous/subcutaneous HMAs was observed in patients receiving treatment beyond 6 months (25.0% vs 17.0%, 18.5% vs 9.0% and 11.4% vs 7.6% for 8, 10 and 12 months, respectively). Mean time to discontinuation of treatment was numerically higher for the oral DEC-C users compared with the IV/SC HMA group (87.7 vs 82.0 days); however, the differences were not statistically significant.

"For many patients living with MDS, the potential for additional costs and time associated with travel for regular infusions can be a significant burden during a stressful time in their lives," said Tehseen Salimi, MD, MHA, Senior Vice President Medical Affairs, Taiho Oncology. "Our goal with this study was to measure the real-world impact of oral therapy. As a leader in the development of orally administered anti-cancer agents, Taiho Oncology is pleased to see how outcomes of this real-world study show some of the potential benefits of an oral therapy in myelodysplastic syndromes."

About the Study

This study was a retrospective analysis using the U.S. Cerner Enviza claims database; medical and prescription claims data for patients were linked to mortality data from Datavant. Adults aged ≥18 years, who were diagnosed with MDS and who had ≥1 claim for an HMA (oral DEC-C or IV/SC HMA) were included. Patients had variable follow-up after the index date and were followed until end of enrollment, death or end of study. Longitudinal persistence was assessed according to the number of cycles of therapy received during follow-up, where a cycle was defined as either 3-10 days of administration of index intravenous/subcutaneous HMA or one claim for oral DEC-C within a 28-day cycle.

About Myelodysplastic Syndromes
Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. In the U.S., approximately 20,000 cases of MDS are reported every year,5 with an overall age-adjusted incidence rate of 4.0 cases per 100,000 population.6 MDS may progress into acute myeloid leukemia (AML) in approximately 30-40% of patients.7,8 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML.

On December 10, 2023 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, reported that the first patient has been dosed in the Phase I PERFORM trial of ATG-031 for the treatment of patients with advanced solid tumors or B-cell non-Hodgkin’s lymphoma (B-NHL), at The University of Texas MD Anderson Cancer Center, the lead center of the study that also includes three other clinical trial centers across the U.S (Press release, Antengene, DEC 10, 2023, View Source [SID1234638385]).

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The PERFORM trial is a first-in-human, multi-center, open-label, Phase I dose-finding study of ATG-031 in patients with advanced solid tumors or B-NHL. The study’s primary objective is to evaluate the safety and tolerability of ATG-031 as a monotherapy, and determine the appropriate dose for Phase II studies. The secondary objective is to characterize the pharmacology, evaluate the immunogenicity, and assess the preliminary efficacy of ATG-031.

"We are delighted that the PERFORM trial has successfully dosed its first patient in the U.S. CD24 is a target with great potential in regulating macrophage activities in tumor environment. Supported by the striking preclinical efficacy demonstrated by blocking CD24 in preclinical studies and a promising preclinical safety profile based on CD24’s limited expression in normal tissue, Antengene has quickly initiated the PERFORM study in the U.S. to further assess the safety and tolerability of ATG-031 in late stage cancer patients," said Dr. Amily Zhang, Antengene’s Chief Medical Officer. "Moving forward, we will continue to work closely with investigators at MD Anderson and three other clinical trial centers in the U.S. to bring clinical benefit to more patients as soon as possible."

"With the joint persistent efforts from Antengene’s internal teams, we have made great strides to the development of ATG-031, a first-in-class anti-CD24 monoclonal antibody targeting the novel ‘don’t eat me’ pathway, while making rapid progress with the clinical development of other core assets. To date, we have established close collaboration with more than 100 clinical trial centers in the U.S., Australia, and the Mainland of China," said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO. "Remaining committed to our global innovation strategies and steadily expediting our clinical programs, we will focus on next generation novel treatments to address broad unmet medical needs post the current immune checkpoint inhibitors."

About ATG-031
ATG-031 is a first-in-class humanized CD24 monoclonal antibody which inhibits the "don’t eat me" signal and enhances macrophage-mediated phagocytosis of cancer cells. Tumor cells evade the surveillance of the human immune system by over-expressing "don’t eat me" surface proteins that signal macrophages to prevent the detection and phagocytosis of cancer cells. CD24 (cluster of differentiation 24) is a prominent "don’t eat me" signal that plays a significant role in tumor immune evasion by suppressing macrophage-mediated phagocytosis. Compared to CD47, another well-known "don’t eat me" target, CD24 has a more restricted distribution in normal tissue and higher expression in cancerous tissue. In addition，unlike CD47，CD24 is not expressed on human red blood cells，allowing for a wider therapeutic window and minimal on-target-off-tumor toxicity as a CD24-targeted therapy.

As a novel innate immune checkpoint, CD24 orchestrates immune evasion through its interaction with the inhibitory receptor Siglec-10 (sialic-acid-binding Ig-like lectin 10) expresses on tumor-associated macrophages (TAMs). Preclinical data presented in 2023 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR 2023) demonstrated that ATG-031 can specifically bind to CD24 with nM affinity and block the interaction of CD24 and Siglec-10. Furthermore, ATG-031 induces efficient phagocytosis with a picomolar EC50 and stimulates the pro-inflammatory cytokines production by macrophages.

On December 10, 2023 Nona Biosciences, a global pioneer of technology innovation and antibody discovery and development solutions, and Evive Biotech, a global biopharmaceutical company devoted to developing a portfolio of novel biological therapies for patients worldwide, reported a collaboration agreement on antibody discovery based on the Harbour Mice antibody technology platform of Nona Biosciences (Press release, Nona Biosciences, DEC 10, 2023, View Source [SID1234638384]). The collaboration brings together professional advantages of Nona Biosciences and Evive Biotech, aiming to accelerate the process of antibody discovery and drug development to benefit patients faster.

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Harbour Mice is a proprietary antibody technology platform that utilizes the transgenic mouse to generate fully human monoclonal antibodies in both a traditional two heavy and two light chain (H2L2) format and a heavy chain only (HCAb) format. This platform holds significant potential for the development of therapeutic antibodies and the acceleration of drug discovery and development.

"Nona Biosciences is committed to bringing antibody discovery and research solutions to our partners better and faster," said Jingsong Wang, MD, PhD, Chairman of Nona Biosciences. "With the capabilities of Harbour Mice, we look forward to empowering our partners in antibody drug discovery and development, and helping more patients benefit from cutting-edge technologies and therapies."

"There is tremendous potential in antibody-based therapy, and I am very excited about this collaboration," said Simon Li, MD, PhD, CEO & CMO of Evive Biotech. "Evive Biotech’s mission is to develop innovative biologic therapies for patients worldwide. We eagerly anticipate collaborating with Nona Biosciences to accelerate the discovery of innovative antibody therapies to benefit patients across the globe."

On December 10, 2023 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported positive initial clinical data from its ongoing Phase 1/2a trial of MP0533, a novel tetra-specific T cell engager, in a poster at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Molecular Partners, DEC 10, 2023, View Source [SID1234638383]). These data, which highlight encouraging initial safety and antitumor activity, expand upon those previously disclosed in the conference abstract.

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"We are excited to share these initial data for MP0533, where we see antileukemic activity, already at these low doses, with a favorable safety profile. We look forward to the continuation of this study and evaluating the full potential of MP0533 for patients," said Patrick Amstutz, CEO of Molecular Partners. "For the first time ever, a non-antibody-based T-cell engager shows clinical activity, opening the door for next-generation DARPin drugs, such as tetra-specifics and logic-gated molecules."

As of the data cut-off (October 24, 2023), 11 patients had been enrolled in the first four dosing regimens (DR) of the ongoing Phase 1/2a trial of MP0533 monotherapy in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS/AML). The trial enrollment remains on track with patients currently being treated in the fifth of seven dose-escalation cohorts planned.

MP0533 continues to demonstrate an acceptable safety profile across all four DRs studied. No dose-limiting toxicities (DLTs) were observed as of data cut-off, and all patients were able to receive their full dose of MP0533. The most frequently reported MP0533-related adverse events were infusion-related reactions and cytokine release syndrome (all Grade 1-2).

Two responders have been observed to date, including a patient achieving complete response (CR) in DR 4 and another patient with morphological leukemia-free state (MLFS) in DR 3 (initially identified as CRi at the time of abstract submission, data cutoff July 2023). These responses are particularly notable for having occurred at dose levels below those predicted for therapeutically relevant activity.

Details of the poster presenting these results from the ongoing Phase 1/2a trial of MP0533 at the 65th ASH (Free ASH Whitepaper) Annual Meeting and Exposition can be found below. The poster will be made available on Molecular Partners’ website after the presentation. For more information on the trial, please visit clinicaltrials.gov (NCT05673057).

Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster 2
Publication Number: 2921
Title: MP0533, a CD3-Engaging DARPin Targeting CD33, CD123, and CD70 in Patients with Relapsed/Refractory AML or MDS/AML: Preliminary Results of a Phase 1/2a Study
Session Location & Date: San Diego Convention Center, Halls G-H; Sunday, December 10, 2023
Presentation Time: 6:00–8:00 pm PT

About MP0533
MP0533 is a novel, avidity-driven, tetra-specific T cell-engaging, half-life extended, DARPin, which simultaneously targets the tumor-associated antigens CD33, CD123 and CD70 as well as the immune activator CD3 on T cells. MP0533’s affinity to each tumor-associated antigen is tuned to preferentially kill AML cells which commonly co-express at least two of these three target antigens whereas most healthy blood cells only express one or none. MP0533’s unique avidity-driven mode of action therefore enables targeted T cell-mediated killing of AML cells while preserving a therapeutic window that minimizes damage to healthy cells.