Amnolake (tamibarotene) / Nippon Shinyaku, Zeria Pharma, RaQualia, Ohara Pharma, Rege Nephro - LARVOL DELTA

Targeting BLVRB Overcomes Immunosuppression and Potentiates Immunotherapy in Monocytic Acute Myeloid Leukemia. (PubMed, Cancer Discov) - "We further demonstrated that the small molecule Tamibarotene targets BLVRB, enhancing the efficacy of both CAR-T and anti-PD-1 antibody therapies in AML. These findings elucidate the critical mechanism regulating immunosuppression in monocytic AML and identify BLVRB as a therapeutic target for improving AML immunotherapy."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • MAFB

Pivotal Results of SELECT-MDS-1 Phase 3 Study of Tamibarotene with Azacitidine in Newly Diagnosed Higher-Risk MDS. (PubMed, Blood Adv) - P3 | "The use of tamibarotene-based therapy to target RARα as a novel approach in HR-MDS pts with RARA gene overexpression is not a paradigm which can augment response rates beyond HMA monotherapy. Further explorations of alternative approaches, including those with a biomarker, to alter the natural history of this disease are warranted."

Journal • P3 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • RARA

Transcriptomic Signatures of Microglial Phagocytosis Reveal Diagnostic Markers and Immune Landscape in Alzheimer's Disease. (PubMed, FASEB J) - "The study further identified two molecular subtypes with distinct immune features, constructed regulatory networks, and predicted potential therapeutics including Tamibarotene. By integrating transcriptomics and machine learning, this study identifies key molecular features of microglial phagocytosis in AD, providing a novel diagnostic framework and insights into the immune mechanisms of the disease."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Inflammation • HLA-DPA1 • IL4R • ITGAM • SPP1 • TNFRSF1B

Integrative Multi-Omics Mendelian Randomization Identifies BLMH as a Keratinocyte-Enriched Protective Candidate Gene and Potential Therapeutic Target in Psoriasis. (PubMed, J Inflamm Res) - "Our integrative multi-omics analysis nominates BLMH as a keratinocyte-enriched protective candidate gene in psoriasis and suggests tamibarotene as a potential repurposed compound for further investigation. However, the experimental validation remains preliminary, and further mechanistic, in vivo, and translational studies are required to validate these findings."

Journal • Dermatology • Immunology • Inflammation • Psoriasis • BLMH • CXCL8 • IL6 • KRT16

Integrative Multi-Omics and Mendelian Randomization Analysis Identify Core Genes and Potent Drug Targets for Insomnia. (PubMed, Curr Neuropharmacol) - "This study identified five core genes, among which HLA-G shows suggestive causal links to insomnia, while the others are supported as promising candidate targets. They show promising diagnostic and drug development value, providing insights into insomnia pathogenesis and a theoretical basis for novel biomarkers and targeted therapies."

Journal • Cardiovascular • CNS Disorders • Depression • Diabetes • Hypertension • Insomnia • Metabolic Disorders • Mood Disorders • Psychiatry • Sleep Disorder • LGALS3 • PIK3CG • S1PR1

A PHASE 2 STUDY OF TAMIBAROTENE AND ARSENIC TRIOXIDE (ATO) FOLLOWED BY GEMTUZUMAB OZOGAMICIN (GO) FOR FIRST RELAPSED ACUTE PROMYELOCYTIC LEUKEMIA: THE JALSG APL219R STUDY (EHA 2026) - "Background In Japan, the standard salvage strategy for relapsed acute promyelocytic leukemia (APL) has been established by the Japan Adult Leukemia Study Group (JALSG) APL205R trial, consisting of arsenic trioxide (ATO) reinduction and consolidation, high-dose cytarabine–based chemotherapy with peripheral blood stem cell collection, followed by autologous hematopoietic stem cell transplantation (auto-HSCT). Summary/Conclusion Despite not reaching the planned sample size, the APL219R study demonstrated a high 1-year EFS with manageable toxicity in this phase 2 cohort of patients with relapsed APL who did not undergo auto-HSCT. These results indicate that a transplant-free strategy may be a clinically meaningful treatment option, particularly for patients who are unsuitable for or lack access to auto-HSCT."

P2 data • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Infectious Disease • Neutropenia • Novel Coronavirus Disease • CD33

Am80 (tamibarotene) and ATRA induce highly similar molecular responses and myeloid differentiation in non-APL AML, enhanced by LSD1/GCN5 inhibition and increased RARA expression. (PubMed, BMC Cancer) - "The study provides evidence that ATRA can be substituted by the more stable Am80 in retinoid-based AML therapies. It also identifies elevated RARA expression as a potential marker for sensitivity to combination therapy with retinoids and epigenetic inhibitors in AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • RARG

Rege Nephro Gains U.S. Orphan Drug Status for ADPKD Candidate Tamibarotene (TipRanks)

Orphan drug • Polycystic Kidney Disease

TAMIBAROTENE, AN AGONIST OF THE RETINOIC ACID RECEPTOR, ATTENUATED RENAL CYST PROGRESSION IN A MOUSE MODEL OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE. (ISN-WCN 2026) - "The only approved clinical drug for ADPKD is Tolvaptan, a vasopressin V2 receptor (V2R) antagonist that blocks vasopressin signaling, a key driver of cyst growth in ADPKD due to the resulting intracellular increase in cyclic adenosine monophosphate (cAMP). Serum blood urea nitrogen (BUN)showed no significant differences among the three groups. The proportion of Ki-67-positive cells in the kidneys was significantly reduced in the 10 mg/kg group.Conclusion Tamibarotene inhibited cyst progression in ADPKD in a dose-dependent manner.The specific mechanisms will be further investigated."

Preclinical • Acute Promyelocytic Leukemia • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Hematological Malignancies • Leukemia • Nephrology • Polycystic Kidney Disease • Renal Disease • PCNA • PKD1 • PRKD1

Few Drug Approvals in MDS: Lessons and Insights from a Decade of Clinical Trials (ICKSH 2026) - "Aside from allogeneic transplantation, the current standard of care approach for higher -risk myelodysplastic syndromes/neoplasms (HR -MDS) remains monotherapy with a hypomethylating agent (HMA) including azacitidine, decitabine, or oral decitabine/cedazurid ine...In this lecture , I will discuss lessons learned from the recently reported negative trials of azacitidine in combination with eprenetapopt (APR -246), magrolimab, pevonedistat, sabatolimab, tamibarotene, and venetoclax...Instead, I will advocate for using the IWG 2023 response criteria to better capture clinically meaningful benefits in HR-MDS. Lastly, I will emphasize the need for the scientific community to access patient -level data and samples from failed phase 3 trials in an efficient and expedited fashion to inform the development of subsequent trials."

Clinical • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • TP53

A Multimodal Diagnostic Model for Hepatocellular Carcinoma Integrating Biomarkers Related to Programmed Cell Death and Radiomics Features. (PubMed, Curr Med Chem) - "We developed a reusable multimodal diagnostic framework with candidate biomarkers and a radiomics tool to facilitate the early detection and risk stratification of HCC."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CAPG • MS4A6A

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Syros Pharmaceuticals | N=80 ➔ 100

Biomarker • Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=155 | Active, not recruiting | Sponsor: Syros Pharmaceuticals | Trial primary completion date: Jun 2020 ➔ Jun 2021

Biomarker • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=155 | Active, not recruiting | Sponsor: Syros Pharmaceuticals | Trial completion date: Dec 2021 ➔ Dec 2022 | Trial primary completion date: Jun 2021 ➔ Nov 2022

Biomarker • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Syros Pharmaceuticals | N=40 ➔ 80

Biomarker • Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Syros Pharmaceuticals | Not yet recruiting ➔ Recruiting

Biomarker • Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=137 | Recruiting | Sponsor: Syros Pharmaceuticals | Trial completion date: Feb 2020 ➔ Dec 2021 | Trial primary completion date: Feb 2019 ➔ Jun 2020

Biomarker • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Syros Pharmaceuticals | Trial primary completion date: Mar 2018 ➔ Aug 2018

Biomarker • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=112 | Recruiting | Sponsor: Syros Pharmaceuticals | Trial primary completion date: Aug 2018 ➔ Feb 2019

Biomarker • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Syros Pharmaceuticals

Biomarker • New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=155 | Completed | Sponsor: Syros Pharmaceuticals | Active, not recruiting ➔ Completed

Biomarker • Trial completion • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

SY-1425-201: A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=155 | Active, not recruiting | Sponsor: Syros Pharmaceuticals | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

CRISPR/Cas9 Screens Implicate RARA and SPNS1 in Doxorubicin Cardiotoxicity. (PubMed, JACC CardioOncol) - "Our study identified numerous drug-gene interactions that illuminate mechanisms underlying DOX-induced cardiotoxicity and provide a technical framework for future functional genomics screens to nominate therapeutic targets and genetic biomarkers."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • RARA

Therapeutic Potential of Amyloid-β Interactors in Rapidly Progressive Alzheimer's Disease-An In Silico Study. (PubMed, Mol Inform) - "Virtual screening of a therapeutic drug library against fumarate hydratase identified several compounds with strong binding affinities, among which quinestrol, estradiol benzoate, norethindrone, tamibarotene, drospirenone, and ketanserin emerged as lead candidates. Together, this work highlights key molecular targets in rpAD and proposes repurposed, pharmacologically diverse compounds with multitarget neuroprotective potential. By utilizing in silico analysis, the study provides a rational framework for target discovery and drug prioritization in rpAD, offering a foundation for future experimental validation and the development of translational research."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42 • FH

Durability of complete response outperforms complete response rates as a surrogate endpoint for advancing to phase III trials in high-risk myelodysplastic syndromes (ASH 2025) - "The HMA plus venetoclax cohort (n=59) had a CRrate of 11.9% (7/59) with 8.5% (5/59) durable CR, equating to 71% (5/7) of CRs durable. Clinical trial pts(n=41) receiving HMA plus novel agents (magrolimab, eprenetapopt, or tamibarotene) had a higher CRrate of 29.3% (12/41) with 24.4% (10/41) durable CR, translating into 83% (10/12) of CRs being durable.In subgroup analysis of pts with TP53-mutated MDS treated with HMA alone (n=242), achieving a durableCR was associated with a 38% reduction in risk of death (HR 0.62; 95% CI 0.39–0.97; p=0.037). Only durable CR translates into a survival benefit in HR-MDS. CR >6 months is a practical, clinicallymeaningful surrogate endpoint and may improve assessment of treatment efficacy and accelerate drugdevelopment in HR-MDS."

Clinical • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • TP53