On December 10, 2023 Dizal reported the full analysis of the multinational pivotal study of golidocitinib for r/r PTCL (JACKPOT8 PART B) in an oral presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (2023 ASH (Free ASH Whitepaper), San Diego) (Press release, Dizal Pharma, DEC 10, 2023, View Source [SID1234638388]). The results were simultaneously published in the prestigious peer-reviewed journal The Lancet Oncology (Impact Factor: 54.4). This follows the publication of the Phase I clinical data of golidocitinib for the treatment of r/r PTCL (JACKPOT8 PART A) in Annals of Oncology (Impact Factor: 51.8) three months ago.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Golidocitinib is currently the first and only Janus kinase 1 (JAK1) selective inhibitor being evaluated for the treatment of r/r PTCL. A total of 104 patients with r/r PTCL were enrolled in the JACKPOT8 PART B study to evaluate the efficacy and safety of golidocitinib as a monotherapy. At the cut-off date of August 31, 2023, per independent review committee (IRC) assessment, 70% of patients achieved target lesion size reduction, yielding an overall response rate (ORR) of 44.3%, and a complete response rate (CRR) of 23.9%. Tumor responses were observed across various PTCL subtypes. The responses were durable, with the median duration of response (mDoR) of 20.7 months. The median progression-free survival (mPFS) was 5.6 months, and the median overall survival (mOS) was 19.4 months and still ongoing. As a potent JAK1 inhibitor with > 200 to 400-fold selectivity over other JAK family members, golidocitinib demonstrated a favorable safety profile. The most common treatment-related adverse events (TRAEs) were reversible and clinically manageable. These findings highlight the potential of golidocitinib to offer robust and durable clinical benefits for patients with r/r PTCL.

"PTCL is a highly heterogeneous and aggressive non-Hodgkin lymphoma (NHL) with the characteristics of various subtypes, high recurrence rate and poor prognosis. Patients with r/r PTCL have limited treatment options and a poor prognosis with a low survival rate. The efficacy of current treatment modalities varies among different r/r PTCL subtypes." said Jun Zhu, MD, PhD at the Department of Lymphoma, Peking University Cancer Hospital and Institute, the correspondence author of the paper, "The JAK/STAT signaling pathway plays a pivotal role in the pathogenesis and progression of various hematologic malignancies, including T-cell malignancies. Consequently, targeting the JAK/STAT pathway emerges as an innovative and highly promising treatment option for PTCL. Golidocitinib is an oral, potent, JAK1 only inhibitor with superior selectivity and favorable pharmacokinetic properties, offers robust and sustained inhibition of the JAK/STAT pathway while maintaining optimal clinical safety."

"In the JACKPOT8 PART B study, more than 100 patients with r/r PTCL were enrolled. The efficacy analysis of 88 patients revealed an ORR of 44.3%, with 23.9% achieving complete response. Notably, a consistently high ORR was observed across various PTCL subtypes. The median DoR for golidocitinib was 20.7 months, mPFS reached 5.6 months, and mOS was 19.4 months." said Yuqing Song, MD, PhD at the Department of Lympho-Oncology of Peking University Cancer Hospital, the lead author of the paper, "Golidocitinib demonstrates superior ORR and survival results as compared to the current available treatment options and offers hope for improving the poor prognosis of patients with r/r PTCL. These findings present innovative therapeutic possibilities and paves the way towards better patient outcomes."

"It is gratifying to see the increasing recognition of golidocitinib’s potential as a new therapy for patients with PTCL." said Xiaolin Zhang, Ph.D., Chairman and CEO of Dizal, "Patients with r/r PTCL have long been facing limited treatment options and a poor prognosis. Golidocitinib stands as a major achievement resulting from Dizal’s dedicated translational science efforts. Its superior efficacy and safety, as demonstrated through compelling global pivotal trials, bring hope for these underserved patients."

These findings, highlighting the superior efficacy and safety of golidocitinib, have been widely acknowledged at prestigious conferences including ASCO (Free ASCO Whitepaper), EHA (Free EHA Whitepaper), ICML, and ASH (Free ASH Whitepaper), with six oral presentations over four consecutive years. In September 2023, the NDA for golidocitinib was accepted by the CDE with Priority Review status for the treatment of r/r PTCL. Dizal continues to expand the scope of clinical research on golidocitinib and explore its application in a broader patient population. At 2023 ASH (Free ASH Whitepaper), Dizal will also announce positive results of golidocitinib as maintenance therapy for patients with PTCL after first-line systemic therapy in a phase 2 study (JACKPOT26).

About golidocitinib (DZD4205)

Golidocitinib is currently the first and only Janus kinase 1 (JAK1) selective inhibitor being evaluated for the treatment of r/r PTCLs. At the data cut-off date of August 31, 2023, Golidocitinib has demonstrated robust and durable anti-tumor activity, with an ORR of 44.3%. More than 50% of the patients with tumor remission achieved a complete response with a CRR of 23.9%. Per IRC assessment, mDoR reached 20.7 months. Golidocitinib was granted Fast Track Designation by the U.S. FDA for the treatment of r/r PTCL in February 2022. In September 2023, the CDE accepted the NDA and granted the Priority Review status for the treatment of r/r PTCL. The Phase I clinical data of golidocitinib for the treatment of r/r PTCL (JACKPOT8 PART A) was published in Annals of Oncology (Impact Factor: 51.8), and global pivotal trials data of golidocitinib for the treatment of r/r PTCL (JACKPOT PART B) was published in The Lancet Oncology (Impact Factor: 54.4).

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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."