Former executives from REGENXBIO have launched Tern Therapeutics, a new biotechnology company targeting two early-stage gene therapies in clinical development for separate symptoms of the ceroid lipofuscinosis type 2 (CLN2) form of Batten disease.
Let’s start with some background.
First things first: Tern debuted on Aug. 27 with $15 million in funding.
- Investment details: The finance was led by ATW Partners, a New York-based investment management company, as well as Steve Oliveira, a biotech investor and head of Nemean Asset Management.
- Note: This financing will be used to fund ongoing clinical testing of the company’s lead asset (TTX-381) as well as advance its therapeutic pipeline.
Now this company.
Founded in 2023, the privately held biotechnology company is working to speed up the development process for a therapeutic pipeline of one-time gene therapy medicines targeting rare diseases.
More specifically: CLN2 disease.
And its leadership?
The company was founded by:
- CEO Alex M. Bailey, PhD
- Previous: REGENXBIO’s Head of Early Program and Portfolio Development
- Chief Medical Officer (CMO) Christina Ohnsman
- Previous: REGENXBIO’s Executive Director of Clinical Development
- Chief Financial and Administrative Officer Matthew Rosini
- Previous: REGENXBIO’s Head of Strategic Initiatives
So I have to ask: Why CLN2 disease?
Typically developing in early childhood, this rare genetic disease impairs motor and mental development, causing epilepsy (seizures), gradually worsening movement disorders, and cognitive decline.
The ocular connection: Vision loss is known to be a significant symptom that usually becomes prevalent in the disease’s later stages, often developing as:
- Progressive retinal dystrophy
- Retinal pigment epithelium (RPE) atrophy
- Peripheral retinal changes
To note: This vision loss is most common among those diagnosed and treated early with enzyme replacement therapy in the brain.
Now let’s dive into these gene therapies.
Keeping with the theme, Tern’s two gene therapy candidates stem from REGENXBIO, which halted their original programs in December 2023:
- TTX-381 (formerly RGX-381)
- Target: ocular manifestations of CLN2 disease
- TTX-181 (formerly RGX-181)
- Target: Central nervous system (CNS) for CNL2 disease
Clinical status: Both gene therapies have received Orphan Drug and Rare Pediatric Disease Designations from the FDA.
Start with TTX-381.
As the company’s most advanced program, this one-time, adeno-associated viral (AAV) vector-based therapeutic is designed to transport a copy of the tripeptidyl peptidase (TPP1) gene—which provides instructions for making the TPP1 enzyme—directly into the retina.
- Note: At least 115 mutations in the TPP1 gene are known to cause CLN2 disease.
Its potential: To create an ongoing supply of TPP1 enzyme to “maintain the health of the retina and address vision loss” in CLN2 disease.
- See a visual of how it works.
Any clinical research on it yet?
That’s ongoing … a first-in-human, dose-label phase 1/2 dose-escalation study is currently being conducted in the United Kingdom on CLN2 patients.
The findings thus far: Reported in June 2024, interim data from Day 30 and Day 90 of follow-up found that four patients injected with TTX-381 demonstrated no serious adverse events (SAEs) or AEs of special interest.
Plus: Aqueous humor (AH) TPP1 sampling “demonstrated robust protein expression in the treated eye with no change from baseline in the fellow eye.”
- At Day 90: “Ellipsoid zone preservation and photoreceptor thickness was greater in the treated eyes compared with control.”
And the conclusions so far?
Investigators have noted TTX-381 to be “well tolerated,” with efficacy data suggesting a “rapid restoration of TPP1 level in the treated eye” and “concomitant preservation of photoreceptors.”
Now TTX-181.
This gene therapy is designed to deliver a working copy of the TPP1 gene to the brain (instead of the retina, as with TTX-381) via the cerebrospinal fluid (CFS).
Its potential: To create an ongoing supply of TPP1 enzyme to “prevent worsening of neurological degeneration” in CLN2 disease patients.
- See a visual of how it works.
And any clinical data on it?
Tern noted that a single-patient, investigator-initiated study was conducted in 2022 on a pediatric patient diagnosed with CLN2 disease at the Hospital de Clinicas in Porto Alegre, Brazil.
As of December 2022, TTX-381 was reported—by REGENXBIO, at the time—to be “well-tolerated” with “no drug-related SAEs.”
So what’s next?
As we mentioned earlier, this $15 million in financing will support the company’s advancement of TTX-381 and its therapeutic pipeline—which means new data in the near future.