A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Orally Administered DF-006 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Multiple Doses of Orally Administered DF-006 in Chronic Hepatitis B Patients

Start Date19 Jul 2023

Sponsor / Collaborator-

ACTRN12621000592842 / CompletedPhase 1

A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Orally Administered DF-006 to Evaluate the Safety, Tolerability, and Pharmacokinetics After a Single Dose and Multiple Doses of Orally Administered DF 006 in Healthy Subjects (Part 1 and Part 2)

Start Date16 Jul 2021

Sponsor / Collaborator-

100 Clinical Results associated with DF-006

100 Translational Medicine associated with DF-006

100 Patents (Medical) associated with DF-006

Literatures (Medical) associated with DF-006

01 Jan 2023·Hepatology

Alpha‐kinase 1 (ALPK1) agonist DF‐006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B

Article

Author: Xu, Tian ; Liu, Danyang ; Yogaratnam, Jeysen ; Chen, Juanjuan ; Wei, Yuning ; Fan, Jieqing ; Wei, Xiong ; Yousif, Ashraf Siddig ; Xu, Cong ; Lichenstein, Henri ; Tuerdi, Aimaier ; Dang, Huaixin ; Zhou, Qiong ; Pan, Yanfang

Background and Aims:In the treatment of chronic hepatitis B (CHB) infection, stimulation of innate immunity may lead to hepatitis B virus (HBV) cure. Alpha‐kinase 1 (ALPK1) is a pattern recognition receptor (PRR) that activates the NF‐κB pathway and stimulates innate immunity. Here we characterized the preclinical anti‐HBV efficacy of DF‐006, an orally active agonist of ALPK1 currently in clinical development for CHB.Approach and Results:In adeno‐associated virus (AAV)‐HBV mouse models and primary human hepatocytes (PHHs) infected with HBV, we evaluated the antiviral efficacy of DF‐006. In the mouse models, DF‐006 rapidly reduced serum HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen levels using doses as low as 0.08 μg/kg, 1 μg/kg, and 5 μg/kg, respectively. DF‐006 in combination with the HBV nucleoside reverse transcriptase inhibitor, entecavir, further reduced HBV DNA. Antiviral efficacy in mice was associated with an increase in immune cell infiltration and decrease of hepatitis B core antigen, encapsidated pregenomic RNA, and covalently closed circular DNA in liver. At subnanomolar concentrations, DF‐006 also showed anti‐HBV efficacy in PHH with significant reductions of HBV DNA. Following dosing with DF‐006, there was upregulation of NF‐κB‐targeted genes that are involved in innate immunity.Conclusion:DF‐006 was efficacious in mouse and PHH models of HBV without any indications of overt toxicity. In mice, DF‐006 localized primarily to the liver where it potently activated innate immunity. The transcriptional response in mouse liver provides insights into mechanisms that mediate anti‐HBV efficacy by DF‐006.

01 Oct 1987·Journal of Allergy and Clinical ImmunologyQ1 · MEDICINE

The prevalence of indoor allergens in the Baltimore area: House dust-mite and animal-dander antigens measured by immunochemical techniques

Q1 · MEDICINE

Article

Author: B. Schwartz ; P.S. Norman ; H. Løwenstein ; M. Newton ; P. Lind

Mattress dust samples from 42 homes in Baltimore, Md., were analyzed by ELISA and rocket immunoelectrophoresis (RIE) for major excrement allergens (P1 [equal to Dp 42], Df 6, and Dm 6) of house dust mites, Dermatophagoides pteronyssinus, D. farinae, and D. microceras, by RIE for cat major epithelial allergen (cat Ag 1) and horse major epithelial antigen (horse Ag 11), and by counter-current immunoelectrophoresis (CCIE) for cat and dog antigens. Dp 42 was detected by ELISA in 24 samples (57%) and Df 6 in 39 samples (92%). All samples were negative to Dm 6. Recorded levels varied from 50 ng of allergen per gram of dust (detection limit) to 15,000 ng/gm. A combined content of Dp 42 and Df 6 greater than 700 ng/gm was associated with a positive reaction in RIE. Concentrations of Dp 42 and Df 6 did not correlate (rS = 0.21; p greater than 0.05). Cat and dog antigens were frequently detected by CCIE (77% and 63%, respectively). CCIE titer to cat correlated well with quantitation of cat Ag 1 by RIE (p less than 0.01). Horse antigen was detected in few homes (5%). None of the specific allergen determinations correlated with levels of human serum albumin determined by RIE.

01 Jan 1985·International Archives of Allergy and Immunology

Relationship between Specific Circulating IgE, Basophil Cell-Bound IgE and Histamine Release Induced by Purified Allergens of Dermatophagoides Farinae

Article

Author: Weyer, A. ; Dandeu, J.P. ; Le Mao, J. ; Rabillon, J. ; David, B.

In this study we analysed the presence and proportions of IgE specific for Df 6 and Df 11 two purified allergens of Dermatophagoides farinae. The characterisation of serum IgE and cell-bound IgE for 3 D. farinae-sensitive patients were performed by CRIE, RAST and PRIST assays. Furthermore the basophils from these same patients were studied by histamine release assays in the presence of Df 6 and Df 11. All the individual patient’s cell and serum IgE samples displayed the presence of IgE antibodies specific for Df 6 and Df 11 but the relative quantities of the IgE for these two specificities were characteristic of each patient. The ratios (Specific IgE for Df 11): (Specific IgE for Df 6) (ratio 11:6) were similar in the serum and on the cells for an individual patient. As judged by histamine release assays, the basophil sensitivities towards Df 6 and Df 11 were very different from one atopic patient to another. Moreover cell sensitivities reflected the proportion of Df 6- and Df 11-specific IgE antibodies found in the serum and in the cell eluate.

News (Medical) associated with DF-006

02 May 2024

·www.biospace.com

Drug Farm Announces anti-HBV immunomodulator, DF-006 is Accepted as a Late-Breaking Presentation at the 2024 European Association for the Study of the Liver Conference

GUILFORD, Conn.--(BUSINESS WIRE)-- Drug Farm, a private biotechnology company utilizing genetics and artificial intelligence technologies to discover and develop innovative, immune-modulating therapies, today announced that the chronic hepatitis B patient data from their Phase 1b trial (ACTRN12621000592842) was accepted as a late breaking poster presentation at the 2024 European Association for the Study of the Liver (EASL) conference that will be held in Milan, Italy between 05 June 2024 to 08 June 2024. Poster #LB46 Title: A phase 1, double-blinded, randomized, placebo-controlled, multicenter global study evaluating the safety, tolerability, and antiviral activity of DF-006 in chronic hepatitis B, virologically-suppressed patients. Date: 05 June 2024 Time: 8.30 am – 5.00 pm CET DF-006 is a first-in-class, orally administered ALPK1 agonist immunomodulator that potently stimulates local, innate immunity in the liver1. DF-006 has successfully completed single and multiple ascending dose (MAD) evaluation in healthy volunteers, and MAD evaluation in virologically suppressed HBeAg negative chronic hepatitis B (CHB) patients. “There remains no effective cure for CHB. DF-006 has a novel mechanism of action that is capable of stimulating the body’s own immune system to help clear the infection. As an oral drug administered once weekly, DF-006 has the potential to be the immunomodulator of choice in combination HBV cure regimens”, said Dr. Ed Gane, Professor of Medicine at the University of Auckland, New Zealand and Chief Hepatologist, Transplant Physician, and Deputy Director of the New Zealand Liver Transplant Unit at Auckland City Hospital. “DF-006 has demonstrated potent antiviral responses in preclinical studies, including inhibition of cccDNA and recruitment of T-cells. The data from this trial study now provides clinical support for a drug with a novel mechanism of action that could be used to help cure CHB patients”, said Drug Farm’s Chief Medical Officer, Dr. Jeysen Yogaratnam. About Drug Farm. Drug Farm is a private biotechnology Company developing innovative treatments targeting innate immunity for hepatitis B, cancer, and autoimmune diseases. Drug Farm's unique IDInVivo platform combines breakthrough technologies in genetics and AI to discover new treatments. IDInVivo technology allows the direct assessment of gene targets in living animals with intact immune systems. Using the IDInVivo platform, Drug Farm has identified novel innate immunity pathways and targets and is now rapidly advancing multiple first-in-class drug candidates into clinical development. For more information please visit: Reference: Xu C, et al. Hepatology. 2023 Jan 1;77(1):275-289. doi: 10.1002/hep.32614. Epub 2022 Sep 17. View source version on businesswire.com: Contacts United States: Henri Lichenstein, Ph.D. Chief Executive Officer Email: hlichens@drug-farm.com China: Tony Xu, Ph.D. Co-founder and Chief Operating Officer Email: tony.xu@drugfarminc.com Source: Drug Farm View this news release online at:

Phase 1Clinical ResultImmunotherapy

15 Jan 2024

·www.pharmaceutical-technology.com

Drug Farm candidate gains rare paediatric disease status

ROSAH syndrome is caused by mutations in the ALPK1 gene. Credit: Gorodenkoff via Shutterstock. Drug Farm has been granted a rare paediatric disease (RPD) designation from the US Food and Drug Administration (FDA) for DF-003 to treat retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache (ROSAH) syndrome. DF-003 is an alpha-kinase 1 (ALPK1) indicated for the treatment of the rare autosomal dominant disorder ROSAH syndrome. The condition is caused by mutations in the ALPK1 gene, characterised by the symptoms listed in its name. ROSAH syndrome currently has no approved treatments. Drug Farm received FDA clearance of its investigational new drug (IND) application to initiate Phase I studies for the candidate in June 2023, after pre-clinical studies in ROSAH syndrome transgenic mouse models showed significant activity and favourable drug-like properties. If a new drug application for DF-003 is approved by the FDA, the company may be eligible to receive a priority review voucher (PRV) that can be redeemed to receive for any later marketing application. The double-blind, placebo-controlled Phase I trial (NCT05997641) is evaluating the safety, tolerability, and pharmacokinetics of DF-003 on 96 healthy subjects. The study is expected to conclude in Q1 2025. The company has other candidates in the pipeline, including another ALPK1 agonist DF-006, which is under investigation in the third part of a Phase I study for the treatment of chronic hepatitis B infection. The trial is assessing the levels of DF-006 and its related compounds in the blood following doses of the formulation. In May 2023, Drug Farm generated $27m in a Series C funding round led by Betta Capital. The company, which has offices in both the US and China, also raised $56m in February 2021 in a Series A lead by BVCF. In the announcement accompanying the designation, Drug Farm’s chief medical officer Jeysen Yogaratnam said: “Obtaining Rare Pediatric Disease Designation recognizes the serious and debilitating complications of this rare disease and upholds our goal to provide DF-003 as the first targeted drug for potential treatment in patients afflicted with ROSAH syndrome.”

Phase 1INDPhase 2

26 Sep 2023

·www.biospace.com

Drug Farm Doses First Patient in Part 3 of Phase 1 Chronic Hepatitis B Trial

Trial will evaluate DF-006, a first-in-class ALPK1 agonist that stimulates local innate immunity in the liver GUILFORD, Conn. & SHANGHAI--(BUSINESS WIRE)-- Drug Farm, a clinical-stage biopharmaceutical company, announced today that it has dosed the first chronic hepatitis B patient in Part 3 of its Phase 1 clinical trial (ANZCTR Trial ID: ACTRN12621000592842). This trial is evaluating Drug Farm’s first-in-class ALPK1 agonist, DF-006, as a monotherapy and in combination with standard-of-care nucleos(t)side reverse transcriptase inhibitors in treatment-naïve and virologically suppressed patients with chronic hepatitis B infection. “DF-006 is a first-in-class innate immunity modulator that has demonstrated potent anti-hepatitis B virus (HBV) responses in in vitro and in vivo preclinical studies as described in our recent publication in Hepatology1,” said Drug Farm’s Chief Medical Officer, Dr. Jeysen Yogaratnam. “We will be evaluating DF-006 in various chronic hepatitis B patient subpopulations in our global multicenter placebo-controlled randomized study at sites in Europe and Asia, including China.” “DF-006 has demonstrated a good safety and tolerability pro date following single and multiple ascending dose evaluations in healthy volunteers,” said Prof. Ed Gane, the lead Principal Investigator for this study. “As an oral drug administered once weekly, DF-006 has the potential to be the immunomodulator of choice in combination HBV cure regimens”. Xu C, Fan J, Liu D, Tuerdi A, Chen J, Wei Y, Pan Y, Dang H, Wei X, Yousif AS, Yogaratnam J, Zhou Q, Lichenstein H, Xu T. Alpha-kinase 1 (ALPK1) agonist DF-006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B. Hepatology. 2023 Jan 1;77(1):275-289. doi: 10.1002/hep.32614. About Drug Farm Drug Farm is a private biotechnology company developing innovative treatments targeting innate immunity for hepatitis B, heart and kidney diseases, and ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache) syndrome. Drug Farm's unique IDInVivo platform combines breakthrough technologies in genetics and AI to discover new treatments. IDInVivo technology allows the direct assessment of gene targets in living animals with intact immune systems. Using the IDInVivo platform, Drug Farm has identified novel innate immunity pathways and targets and is now rapidly advancing multiple first-in-class drug candidates into clinical development. For more information please visit: View source version on businesswire.com: Contacts United States: Henri Lichenstein, Ph.D. Chief Executive Officer hlichens@drug-farm.com China: Tony Xu, Ph.D. Chief Operating Officer tony.xu@drugfarminc.com Source: Drug Farm View this news release online at:

Phase 1

100 Deals associated with DF-006

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis B, Chronic	Phase 1	AU	Zhejiang YaoYuan Biotechnology Co., Ltd.	13 Sep 2023
Hepatocellular Carcinoma	Phase 1	-	Shanghai Drug Farm Biological Technology Co., Ltd.Startup	-

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