farudodstat (ASLAN003) / Almirall, ASLAN Pharma - LARVOL DELTA

Transcriptome analysis reveals the mechanism of cortisol through GR regulating the expression of inflammatory cytokines in Siberian sturgeon (Acipenser baerii) after LPS treatment in vitro. (PubMed, Fish Shellfish Immunol) - "Subsequently, the inflammation-related genes of the AbGR antagonistic group (LPS + cortisol + RU-486) and the AbGR non-antagonistic group (LPS + cortisol) were compared by qRT-PCR and high-throughput sequencing methods. Furthermore, an AP-1 agonist ASLAN003 was used to detect the regulatory effect of the AP-1 gene on inflammatory cytokines...In this situation, the expressions of il-10 and tgf-β1 were significantly increased, and the expressions of tnf-α and cox-2 were significantly decreased after cortisol treatment. Therefore, this study demonstrated that cortisol inhibits the expression of AP-1 through GR in Siberian sturgeon, and then regulates the generation of the inflammatory response."

Journal • Preclinical • Inflammation • CXCL8 • FOSL1 • IL10 • IL17C • IL1B • IL6 • TGFB1 • TNFA

Invasive lobular carcinoma integrated multi-omics analysis reveals silencing of Arginosuccinate synthase and upregulation of nucleotide biosynthesis in tamoxifen resistance. (PubMed, bioRxiv) - "Treating TAMR cell with Decitabine, a demethylating agent, or Farudodstat, a pyrimidine biosynthesis inhibitor, markedly augmented efficacy of tamoxifen. Restoring ASS1 expression or inhibiting pyrimidine biosynthesis restored tamoxifen sensitivity. ASS1 could be a potential biomarker and therapeutic target in tamoxifen resistant ILC patients, warranting further investigation."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ASS1 • CDH1 • PAICS • PRPS1

Multi omics reveals silencing of Argininosuccinate synthase and upregulation of nucleotide biosynthesis in tamoxifen resistance invasive lobular carcinoma (SABCS 2024) - "Pretreatment with decitabine or combined treatment with DHOD inhibitor Farudodstat, increased growth inhibitory effect of tamoxifen in TAMR cells. Our study unveils ASS1 downregulation as a novel mechanism underlying acquired resistance to tamoxifen and establishes a metabolic link between ASS1 and nucleic acid biosynthesis. Methylation mediated silencing of ASS1 is prompted when estrogen signaling is blocked, diverting one of its substrates, aspartic acid, to nucleic acid biosynthesis and facilitating cell growth. Significance: These findings offer potential therapeutic strategies to overcome tamoxifen resistance by either ASS1 demethylation or targeting nucleic acid biosynthesis, thereby improving treatment outcomes for ILC patients."

Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • ASS1 • CDH1 • PAICS • PRPS1

A novel human disease model of alopecia areata to evaluate benefit of the DHODH inhibitor farudodstat (AAD 2024) - "In addition, farudodstat did not induce catagen, nor did it cause cytotoxicity, affect keratinocyte proliferation, or IP marker expression in healthy HFs. These preliminary data demonstrate anti-CD3/CD28 treatment induced features of AA in an ex vivo disease model and provide promising evidence for the therapeutic potential of farudodstat in patients suffering from AA."

Alopecia • Immunology • IFNG

ASLAN Pharmaceuticals Receives Favorable Opinion From the European Patent Office on Composition of Matter Patent Application for Farudodstat (GlobeNewswire) - "ASLAN Pharmaceuticals Ltd...today announced it has received a favorable patentability opinion from the European Patent Office (EPO) acting as the International Examiner on a polymorph patent application for farudodstat which, if granted in the national stages, will extend effective patent protection for farudodstat until at least 2043....ASLAN is currently conducting a Phase 2a proof-of-concept trial in AA (the 'FAST-AA Study') and an interim readout from the study is expected mid-2024."

P2a data • Patent • Alopecia • Dermatology • Immunology

FAST-AA: Investigate the Efficacy and Safety of Farudodstat Compared With Its Placebo in Adult Alopecia Areata Participants (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: ASLAN Pharmaceuticals | Phase classification: P2a ➔ P2 | Trial completion date: Apr 2024 ➔ Oct 2024 | Trial primary completion date: Feb 2024 ➔ Sep 2024

Phase classification • Trial completion date • Trial primary completion date • Alopecia • Immunology

Exploring the therapeutic potential of DHODH inhibitor farudodstat for alopecia areata treatment in a novel ex vivo model of human hair follicle immune privilege collapse (ISDS 2023) - "Preliminary results show that anti-CD3/CD28 treatment in this ex vivo model can successfully stimulate T-cell proliferation, which subsequently induces key features of AA, including stimulation of MHC I and II expression in the bulb. Additionally, our data suggest that farudodstat might protect HFs from IP collapse and offer a novel therapeutic approach for AA."

IO biomarker • Preclinical • Alopecia • Immunology • Inflammation • IFNG

Exploring the therapeutic potential of DHODH inhibitor farudodstat for alopecia areata treatment in a novel ex vivo model of human hair follicle immune privilege collapse (EADV 2023) - "Our preliminary results show that anti-CD3/CD28 treatment in this ex vivo model can successfully stimulate T cell proliferation, which subsequently induces key features of AA including upregulation of MHC I and II as markers of IP collapse. Additionally, our data suggest that farudodstat might protect from IP collapse and offer a novel therapeutic approach for AA, which deserves further pre-clinical investigation."

IO biomarker • Preclinical • Alopecia • Inflammation • IFNG

Exploring the therapeutic potential of DHODH inhibitor farudodstat for alopecia areata treatment in a novel ex vivo model of human hair follicle immune privilege collapse (EADV 2023) - "Our preliminary results show that anti-CD3/CD28 treatment in this ex vivo model can successfully stimulate T cell proliferation, which subsequently induces key features of AA including upregulation of MHC I and II as markers of IP collapse. Additionally, our data suggest that farudodstat might protect from IP collapse and offer a novel therapeutic approach for AA, which deserves further pre-clinical investigation."

IO biomarker • Preclinical • Alopecia • Inflammation • IFNG

FAST-AA: Investigate the Efficacy and Safety of Farudodstat Compared With Its Placebo in Adult Alopecia Areata Participants (clinicaltrials.gov) - P2a | N=60 | Recruiting | Sponsor: ASLAN Pharmaceuticals

New P2a trial • Alopecia

A novel ex vivo model of human hair follicle immune privilege collapse reveals thepotential of farudodstat, a DHODH inhibitor, as a therapeutic for alopecia areatatreatment (ISID 2023) - "Treatment with 140 nM farudodstat significantly reducedthe proliferation of T-cells, abrogated MHC protein expression, and also reduced thenumber of MHC II+ cells in the hair bulb. Of note, farudodstat treatment alone did notpromote catagen induction and did not affect hair matrix keratinocyte proliferationor IP markers, suggesting no signs of cytotoxicity in healthy microdissected HFs.Our preliminary results show that T-cell activation via anti-CD3/CD28 treatment inthe ex vivo model can successfully induce key features of AA including IP collapse.Additionally, our data suggest that the DHODH inhibitor farudodstat may protect fromIP collapse and offer a novel therapy for AA."

IO biomarker • Late-breaking abstract • Preclinical • Alopecia • Inflammation • IFNG

ASLAN Pharmaceuticals Announces Four Abstracts on Eblasakimab and Farudodstat, Including Two Late-Breakers, to be Presented at the 1st International Societies for Investigative Dermatology Meeting (GlobeNewswire) - "ASLAN Pharmaceuticals...announced the acceptance of two late-breaker abstracts - one on eblasakimab and one on farudodstat – for presentation at the 1st International Societies for Investigative Dermatology (ISID) Meeting, which will take place from May 10 to 13, 2023, in Tokyo, Japan. Two further abstracts on eblasakimab, which were earlier accepted for presentation at the ISID meeting, have been published online in the Journal of Investigative Dermatology."

Clinical data • P1 data • Preclinical • Alopecia • Atopic Dermatitis • Immunology

ASLAN Pharmaceuticals to Host Virtual Research and Development Day on Novel DHODH Inhibitor Farudodstat for Alopecia Areata (GlobeNewswire) - “ASLAN Pharmaceuticals…announced that it will be hosting a virtual research and development day on Thursday, March 16, 2023, from 10:00 am – 11:30 am ET….ASLAN’s leadership team…will then provide an update on its recently announced clinical program to investigate farudodstat…in a Phase 2 proof-of-concept trial, as a potential first-in-class treatment for AA….ASLAN plans to initiate a proof-of-concept study of farudodstat in AA in the second quarter of 2023.”

New trial • Trial status • Alopecia • Dermatology • Immunology

ASLAN003, a Novel and Potent Dihydroorotate Dehydrogenase (DHODH) Inhibitor, Induces Differentiation of Acute Myeloid Leukemia (ASH 2018) - P2a; "ASLAN003 prolongs survival and shows therapeutic effects in mice bearing different AML cell lines and reduces leukemic burden in an AML PDX model. Currently, ASLAN003 efficacy is being evaluated in a Phase IIa clinical trial in patients with AML (NCT03451084; Ting, ASH abstract 2018)."

Acute Myelogenous Leukemia • Biosimilar • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology

"$ASLN ASLAN Pharmaceuticals to Host Virtual Research and Development Day on Novel DHODH Inhibitor Farudodstat for Alopecia Areata https://t.co/uTYZQStp3B" (@stock_titan)

Alopecia

Discovery of potent human dihydroorotate dehydrogenase inhibitors based on a benzophenone scaffold. (PubMed, Eur J Med Chem) - "Herein, eighteen teriflunomide derivatives and four ASLAN003 derivatives were designed and synthesized as novel hDHODH inhibitors based on a benzophenone scaffold. Furthermore, 7d exhibited favorable safety profiles in mice and displayed effective antitumor activities with tumor growth inhibition (TGI) rates of 58.3% and 42.1% at an oral dosage of 30 mg/kg in Raji and HCT116 cells xenograft models, respectively. Taken together, these findings provide a promising hDHODH inhibitor 7d with potential activities against some tumors."

Journal • Oncology

ASLAN Pharmaceuticals Reports First Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "ASLAN Pharmaceuticals...announced financial results for the first quarter ended March 31, 2022, and provided an update on recent corporate activities....Anticipated upcoming milestones: Initiation of Phase 2 study of farudodstat, also known as ASLAN003, in inflammatory bowel disease is planned for the first half of 2022.New data on biomarkers and patient reported outcome measures from the Phase 1b proof-of-concept study of eblasakimab expected in the second half of 2022. Topline data from the Phase 2b TREK-AD study of eblasakimab is expected in the first half of 2023."

Commercial • New P2 trial • P2 data • Atopic Dermatitis • Dermatology • Immunology • Inflammatory Bowel Disease

ASLAN Pharmaceuticals Reports Second Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "Farudodstat (ASLAN003): In June, based on emerging clinical data for DHODH inhibitors in inflammatory bowel disease, the Company decided to prioritize the further development of farudodstat in autoimmune skin diseases. A clinical development plan is being finalized and a Phase 2 trial is expected to commence in the first half of 2023."

New P2 trial • Immunology • Inflammatory Bowel Disease

Inhibitors of dihydroorotate dehydrogenase cooperate with Molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication. (PubMed, iScience) - "DHODH inhibitors increased the antiviral efficiency of Molnupiravir not only in organoids of human lung, but also in Syrian Gold hamsters and in K18-hACE2 mice. Combining Molnupiravir with DHODH inhibitors may thus improve available therapy options for COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ASLAN Pharmaceuticals and IQVIA Biotech Enter Into Strategic Collaboration (GlobeNewswire) - "ASLAN Pharmaceuticals...today announced the appointment of IQVIA Biotech...as its preferred clinical research organization for logistics related to decentralized clinical trials, including the global oversight, expansion and engagement of patients for trials related to the clinical development of ASLAN004 and ASLAN003. IQVIA Biotech will provide patient recruitment, clinical monitoring, medical writing and biostatistics for ASLAN’s upcoming 300-patient Phase 2b trial of ASLAN004 in adults with moderate-to-severe atopic dermatitis....IQVIA Biotech is also positioned to collaborate with ASLAN’s clinical operations team on the future development plans for ASLAN003 in inflammatory bowel disease (IBD), with clinical trials commencing early next year. Enrollment of the first patient in the ASLAN004 Phase 2b trial is expected in the fourth quarter of 2021."

Enrollment status • Licensing / partnership • New P2b trial • New trial • Atopic Dermatitis • Immunology • Inflammatory Bowel Disease

ASLAN Pharmaceuticals Reports Third Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Anticipated upcoming milestones...Initiation of Phase 2 trial of ASLAN003 in inflammatory bowel disease expected in the first half of 2022."

New P2 trial • Immunology • Inflammatory Bowel Disease

Preliminary Results of a Phase 2a Dose Optimization Study of ASLAN003 (DHODH inhibitor) in Acute Myeloid Leukemia (AML) Patients Who Are Ineligible for Standard Therapy; Early Signs of Activity (ASH 2018) - P2a; "Safety, PK and efficacy data will be updated at the time of presentation. Clinical trial information: NCT03451084"

Clinical • P2a data • Acute Myelogenous Leukemia • Biosimilar • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology

A phase IIA dose optimization study of ASLAN003 in acute myeloid leukemia (AML) (ESMO 2018) - P2a; "Overall AML response data will be listed and summarized showing frequency and proportion of the best response, OCRR and CBR by dose levels. Concentrations and PK parameters will be listed and summarized using descriptive statistics."

P2a data • Acute Myelogenous Leukemia

A Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia (clinicaltrials.gov) - P2a; N=24; Completed; Sponsor: Aslan Pharmaceuticals; Recruiting ➔ Completed; N=56 ➔ 24

Enrollment change • Trial completion • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Neutropenia • Oncology

ASLAN Pharma Secures Debt Funding Of $45M To Support ASLAN003 Development (Benzinga) - "Under the terms of the facility, K2HV will provide ASLAN up to $45 million of secured debt financing consisting of a $20 million initial term loan funded at closing, with the remaining $25 million subject to specific terms and conditions. Proceeds will be used to advance the clinical development of ASLAN003...ASLAN expects to initiate a Phase 2 clinical trial for ASLAN003 in inflammatory bowel disease in early 2022."

Financing • New P2 trial • Immunology • Inflammatory Bowel Disease