Published in Pipeline

Drug Farm receives FDA IND clearance for ROSAH syndrome candidate

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5 min read

The FDA has cleared Drug Farm’s investigational new drug (IND) application for its investigational candidate DF-003 for clinical evaluation of patients with retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome.

Quick rundown on this company, please.

Founded in 2015 and based in Shanghai, China—with U.S. operations in Guilford, Connecticut—Drug Farm (also known as Shanghai Yao Yuan Biotechnology Ltd.) is a private clinical-stage biotech company developing first-in-class therapeutics via proprietary platform mouse genetics and artificial intelligence (AI) technologies.

Its current pipeline includes the following therapeutic areas:

  • Hepatitis B
  • Cancer (hepatocellular)
  • Cardio-renal disease
  • ROSAH syndrome (our topic of interest)
  • Colitis
  • Alzheimer’s disease

How do these platforms work?

First: Both platforms are built using the company’s proprietary piggyBac transposon (ie: DNA segment) technology developed by founder and chair Tian Xu, PhD.

The company’s IDInVivo+ technology uses genetic screens to directly identify novel drug targets present in living animals with intact immune systems (such as healthy mice) and generate a library of genetic mutations.

MedChem5, its AI program, is an integrated platform that uses multiple novel neural networks—such as supervised, active, and reinforcement learning—to allow for rapid medicinal chemistry development. See here (and scroll down) for a visual.

  • The result: The development of first-in-class drugs (such as DF-003)

Now explain ROSAH syndrome.

First documented in 2012 (and officialized in 2019), ROSAH is a relatively new and rare genetic (autoinflammatory) disease and autosomal-dominant disorder that’s characterized by the five aforementioned conditions.

Based on prior research, this disease has been shown to affect patients’ visual function via three main ophthalmic manifestations:

  • Optic nerve involvement
  • Intraocular inflammation (cystoid macular edema)
  • Retinal degeneration

And what causes it?

To be very specific: A mutation within the alpha-kinase gene (ALPK1), whose main function includes producing the ALPK1 protein (which alerts the innate immune system when the presence of bacteria is detected in the body).

  • The result of this: inflammation

The mutation can be inherited from a parent and affects either gender; unfortunately, ROSAH patients have a 50% chance of passing the mutation on to their own children.

Most importantly: Are there any treatments available yet?

While current treatments seek to treat the symptoms of the disease, none have succeeded in targeting the genetic root cause of the disease.

That’s where Drug Farm’s latest investigational candidate comes in.

Gotcha. So tell me about DF-003.

Granted a Rare Pediatric Disease Designation (RPDD) by the FDA in January 2024, DF-003 is an orally-administered, potent, highly-selective inhibitor of the ALPK1 mutation.

How it works: The therapeutic is reported to inhibit the immune inflammatory response, such as that observed in ROSAH syndrome patients.

Its targets: renal disease, cardiovascular disease, and ROSAH syndrome.

Any clinical data on it?

Yes, actually. It recently completed clinical evaluation via a two-part phase 1 study (NCT05997641) to assess its safety, tolerability, and pharmacokinetics (PK; drug metabolism, in other words) in healthy patients.

Go on …

The double-blind, randomized, placebo-controlled, first-in-human (FIH) trial evaluated DF-003 following oral administration as both single and multiple doses in 96 participants.

Why choose healthy patients: Investigators sought to establish a preliminary safety and PK profile for the therapeutic.

However: The ultimate goal for the study was to determine DF-003’s ability to treat chronic kidney disease—not ROSAH syndrome.

And the findings?

According to the company, the phase 1 data supported the use of a once-a-day (QID) oral dosing regimen.

What does that mean for ROSAH syndrome patients?

These findings will be used in an upcoming open-label, single-arm, single-dose, phase 1b study (NCT06395285) focused on using DF-003 for 12 ROSAH patients.

The breakdown: Participants will be orally administered DF-003 QID for 28 days (4 weeks) and followed for up to 8 weeks after the last dosing.

The doses:

  • Loading dose: 140 mg (Days 1, 2, and 3)
  • Maintenance dose: 45 mg QID (starting Day 4-Day 28)

And what will be measured?

Primary outcomes include treatment-emergent adverse events (TEAEs) and serious adverse events (AEs), measured from baseline to Day 78 (±2) days.

See here for secondary outcomes.

So when can we expect data from this study?

Per Clinical Trials, the trial kicked off earlier this month and is expected to conclude in November 2025.

Stay tuned for interim data in the meantime …

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