Tern Therapeutics Selected by US FDA to Participate in the CDRP Program to Expedite CMC Development of TTX-381 to Treat Vision Loss in CLN2 Disease

• Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) program is designed to speed CMC development of promising therapies to enable earlier patient access

• TTX-381 was previously awarded Regenerative Medicine Advance Therapy (RMAT) and Fast Track Designations by the US FDA

Tern Therapeutics, LLC (“Tern”), a biotechnology company developing transformative one-time gene therapies for rare diseases, today announced that TTX-381, the company’s investigational therapy to treat the ocular manifestations of CLN2 disease, has been selected by the U.S. Food and Drug Administration (FDA) to participate in the Chemistry, Manufacturing and Controls (CMC) Development and Readiness Pilot (CDRP) Program. The CDRP program was created by the FDA to facilitate CMC readiness for a limited number of promising therapies with accelerated clinical development timeframes based on the anticipated clinical benefits of earlier patient access. Through the CDRP program, Tern plans to continue to collaborate closely with the FDA to expedite commercial manufacturing readiness of TTX-381.

“Our top priority is getting safe and effective therapies for CLN2 disease to patients as quickly as possible. Partnering with the FDA through the CDRP program will help ensure that late-stage commercial manufacturing for TTX-381 keeps pace with our accelerated clinical development,” said Alex M. Bailey, PhD, CEO of Tern.

FDA selected TTX-381 for the CDRP program based on three main criteria: (1) anticipated clinical benefits of earlier patient access to TTX-381, (2) novelty of TTX-381 and complexity of manufacturing processes, and (3) ability to align CMC development and readiness within the same overall clinical development timespan. Key benefits of the CDRP program include increased communication with the FDA via two additional CMC-focused Type B Meetings as well as opportunity for follow-up CMC-focused discussions, and an expansion of the FDA CMC and Quality teams supporting TTX-381 who are tasked with implementing science- and risk-based regulatory approaches. About TTX-381 TTX-381 is a novel one-time AAV gene therapy designed to deliver a working copy of the TPP1 gene directly to the retina to provide a durable source of TPP1 to maintain the health of the retina and address vision loss in people with CLN2 disease. Vision loss in CLN2 disease rapidly progresses to blindness, and there is currently no available treatment for the ocular manifestations of CLN2 disease. The open-label clinical trial to evaluate the safety and efficacy of TTX-381 is active and recruiting patients in an expansion cohort. Learn more at euclinicaltrials.eu (EUCT number: 2025-521175-31-00) and clinicaltrials.gov (NCT05791864).

Tern Therapeutics Presents Positive Twelve-Month Data from Dose Escalation Cohorts in Phase I/II Trial of TTX-381

• No SAEs related to study drug or administration procedure during 1+ year follow-up

• Rapid, durable, and dose-dependent increases in TPP1 transgene levels to therapeutic range

• Photoreceptor preservation in all treated eyes

• 12-month control period for participants in Cohorts 1 and 2 is complete; enrollment in expansion cohort is underway

Tern Therapeutics, LLC (“Tern”), a biotechnology company developing transformative one-time gene therapies for rare diseases, reported positive twelve-month clinical data relating to the safety and efficacy of its TTX-381 program at the 19th International Congress on Neuronal Ceroid Lipofuscinosis (NCL) in Queensland, Australia.

"While enzyme replacement therapy is available for treatment of central nervous system manifestations of CLN2 disease, allowing children with CLN2 to live longer and better lives, rapid vision loss remains a high unmet need in this population" said Christina Ohnsman, M.D., Chief Medical Officer of Tern, who presented the data at NCL. "The safety and efficacy data presented today support that TTX-381, a one-time gene therapy, is a promising treatment that may prevent further vision loss in these children. We look forward to concluding enrollment of our expansion cohort and learning more about TTX-381."

TTX-381 Phase I/II Clinical Trial Data
An open-label, dose-escalation study of TTX-381 is ongoing with clinical trial sites in the United Kingdom and Germany. One-year data were presented from the Phase I/II portion of the clinical trial, including 6 participants across two dose level cohorts, 2.0x1010 GC (genome copies) per eye (Cohort 1; n=3) and 6.0x1010 GC per eye (Cohort 2; n=3). The dose escalation cohorts are fully enrolled, and enrollment in an expansion cohort is ongoing.

Safety and Tolerability
As of the data cut-off on August 31, 2025, TTX-381 was reported to be well tolerated across both cohorts at Dose Level 1 (2x1010 GC/eye; n=3) and Dose Level 2 (6x1010 GC/eye; n=3) with no serious adverse events (SAEs) related to the drug or subretinal administration procedure in the six participants. Time of post-administration follow-up included a minimum of 12-months for all 6 participants.

TPP1 Concentration in Aqueous Humor (AH)
In CLN2 Batten disease, tripeptidyl peptidase 1 (TPP1) deficiency results in degeneration of nerve cells, particularly in the brain and retina. In the ongoing TTX-381 clinical trial, TPP1 levels in AH are measured using a validated bioanalytical immunoassay at baseline and on Days 30, 90, and 360 post-administration, and levels are compared to baseline, untreated fellow eyes, and samples from healthy non-CLN2 donors. All participants had either undetectable or trace concentrations of TPP1 in both the treated and untreated fellow eyes at baseline, and TPP1 levels rapidly increased in treated eyes by Day 30. By Day 90 post-administration of TTX-381, five of six participants’ treated eyes had AH TPP1 levels that reached or exceeded the normative reference range established in healthy non-CLN2 donors, and levels were maintained through Day 360 (last time point available). TPP1 levels in AH at Day 90 were 28-fold higher in treated eyes administered Dose Level 2 compared with Dose Level 1, demonstrating a dose-dependent response to TTX-381. Untreated eyes continued to have undetectable or trace concentrations of TPP1 in all participants at all timepoints.

Anatomic Data from SD-OCT Imaging
Evidence indicates that photoreceptor degeneration, the cause of vision loss in CLN2 patients, is strikingly symmetrical in both eyes and first detectable in the ellipsoid zone (EZ). Area of EZ loss has been recognized to be a clinically meaningful surrogate for vision loss, with areas of EZ loss corresponding closely with blind spots in the visual field. Longitudinal SDOCT imaging was performed to evaluate photoreceptor health, specifically the area of EZ loss as well as the thickness of the photoreceptor layer in the central retina. While photoreceptors continued to degenerate rapidly in untreated eyes, these retinal cells were preserved in treated eyes through Day 360. Specifically, area of EZ loss resolved (improved) in 2/6 treated eyes, remained stable in 2/6 treated eyes, and had a small increase (~ 2-fold) in 1/6 treated eyes at Day 360, as compared with baseline. In contrast, area of EZ loss in untreated eyes enlarged by 5- to 27-fold compared with baseline at 1 year. One participant did not have sufficient EZ loss in either eye at Day 360 to evaluate the difference from baseline. Central photoreceptor layer thickness remained stable or increased (improved) in 6/6 treated eyes at Day 360 compared with baseline, in contrast with progressive photoreceptor layer thinning (worsening) in 6/6 untreated eyes. The difference between each pair of treated and fellow, untreated eyes in change from baseline in central photoreceptor layer thickness ranged from 20-92% at 1 year.

About TTX-381
TTX-381 is an investigational one-time AAV9 gene therapy designed to deliver a working copy of the TPP1 gene directly to the retina to provide a durable source of TPP1 to maintain the health of the retina and address vision loss in people with CLN2 disease. Vision loss in CLN2 disease rapidly progresses to blindness, and there is currently no available treatment for the ocular manifestations of CLN2 disease. The open-label clinical trial designed to evaluate the safety and efficacy of TTX-381 is active and enrolling participants in an expansion cohort. Learn more at euclinicaltrials.eu (EUCT number: 2025-521175-31-00) and clinicaltrials.gov (NCT05791864).

Tern Therapeutics Opens New TTX-381 Clinical Trial Site at UKE in Hamburg, Germany

• First clinical trial site for Tern Therapeutics in the European Union

• Approval of CTA from Germany’s federal health authority PEI

Tern Therapeutics, LLC (“Tern”), a biotechnology company developing transformative one-time gene therapies for rare diseases, today announced the approval of a clinical trial application (CTA) from Germany’s federal health authority, Paul-Ehrlich-Institut (PEI), and the opening of a second clinical trial site to evaluate the safety and efficacy of TTX-381, its novel one-time gene therapy candidate for the treatment of the ocular manifestations of CLN2 Batten disease. The newly initiated site is University Medical Center Hamburg Eppendorf (UKE) in Hamburg, Germany, a leading global center for the study and treatment of Batten disease.

UKE is the second clinical trial site for the ongoing TTX-381 study, joining Great Ormond Street Hospital (GOSH) in the United Kingdom. Both UKE and GOSH have world-renowned experts that provide specialized and comprehensive care for patients with CLN2 disease and have conducted pioneering research in the development of new therapies. As the center with the largest cohort of CLN2 patients worldwide, UKE has conducted many studies of the natural history, evaluation, and response to treatment of this rare, progressive neurodegenerative disorder. "The UKE team have been long-time collaborators on the TTX-381 and TTX-181 programs. We are thrilled to welcome them as a TTX-381 clinical trial site and look forward to deepening our partnership with them in bringing this desperately needed treatment to children living with CLN2," said Christina Ohnsman, MD, Chief Medical Officer of Tern. “We are also profoundly grateful to the GOSH team for their ongoing commitment to enrolling this trial with unprecedented speed.”

"We are excited to become a study center for TTX-381, an innovative gene therapy designed to prevent blindness in children with CLN2 disease. This one-time treatment delivers a functional TPP1 gene directly to the retina, offering hope to young patients facing progressive vision loss. As a leading European center for CLN2 research, we are proud to contribute to this groundbreaking trial and bring potential new treatment options to the children and families we serve,” said Dr. Angela Schulz, MD, PhD, Head of the Research Group for Childhood Neurodegenerative Disease of UKE and Principal Investigator for the UKE site. The open-label clinical trial designed to evaluate the safety and efficacy of TTX-381 is active and recruiting participants. Learn more at euclinicaltrials.eu (EUCT number: 2025-52117531-00) and clinicaltrials.gov (NCT05791864).

U.K. MHRA Awards Tern Therapeutics Innovation Passport for TTX-381 to Accelerate Gene Therapy for the Treatment of the Ocular Manifestations of CLN2 Disease

• MHRA granted Tern Therapeutics’ TTX-381 an Innovation Passport under the accelerated Innovative Licensing and Access Pathway (ILAP)

• ILAP is designed to optimize the development and expedite the evaluation of innovative medicines for patients with high unmet need

• TTX-381 has also previously been granted Regenerative Medicine Advance Therapy (RMAT) and Fast Track Designations by the U.S. Food and Drug Administration (FDA)

Tern Therapeutics, LLC (“Tern”), a biotechnology company developing transformative one-time gene therapies for rare diseases, today announced that TTX-381 has been awarded the Innovation Passport, the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) innovative medicine designation. TTX-381 is a novel one-time investigational gene therapy product being developed for the treatment of the ocular manifestations of CLN2 disease, a form of Batten disease.

“The CLN2 community urgently needs treatment for the loss of vision caused by CLN2 disease,” said Alex Bailey, Ph.D., Chief Executive Officer of Tern. “Following the recent RMAT and Fast Track designations of TTX-381 by the FDA, the Innovation Passport designation from the MHRA underscores our commitment to delivering TTX-381 to patients around the world as quickly as possible. We look forward to continued collaborations with U.K. health authorities to help us achieve this goal.”

“We are pleased with the rapid progress we have made enrolling the TTX-381 clinical trial at Great Ormond Street Hospital (GOSH) and the promising results emerging from the study,” said Robert Henderson, MD. “ILAP designation highlights the key role of the MHRA and our team at GOSH in developing this product and accelerating its availability to people around the world living with CLN2.”

The Innovation Passport is the entry point to the ILAP, which aims to accelerate time to market for transformative new medicines and facilitate patient access to medicines in the U.K. This designation provides Innovation Passport holders with the opportunity to work more closely with the MHRA and its partner agencies, including the National Institute for Health and Care Excellence (NICE), and grants access to numerous programs designed to support innovative products, such as Joint Scientific Advice with MHRA, NICE, and other partners as needed, as well as priority scheduling for key regulatory and Health Technology Assessment support services. Other benefits of ILAP include the potential for a 150-day accelerated Marketing Authorization Application assessment, a rolling review, and a continuous risk-benefit assessment.

MHRA awarded TTX-381 the Innovation Passport based on three criteria: that the condition addressed is seriously debilitating with a significant unmet clinical need; it is innovative; and that it has the potential to substantially improve patient health outcomes.

Tern Therapeutics Receives US FDA Regenerative Medicine Advanced Therapy Designation for Gene Therapy for the Treatment of the Ocular Manifestations of CLN2 Disease

• Recognizes potential of TTX-381 to address significant unmet need and enables increased dialogue with FDA throughout the development process

• RMAT designation granted following FDA review of initial clinical safety and efficacy data from the ongoing Phase 1/2 study of TTX-381 in CLN2 disease, a form of Batten disease

Tern Therapeutics, LLC (“Tern”), a biotechnology company developing transformative one-time gene therapies for rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to TTX-381. TTX-381 is a novel one-time gene therapy product being developed for the treatment of the ocular manifestations of CLN2 disease, a form of Batten disease.

“This RMAT designation represents another meaningful milestone for Tern and underscores the momentum and strength of our TTX-381 program,” said Alex Bailey, Ph.D., Chief Executive Officer of Tern. “We look forward to continued engagement with the FDA as we work to accelerate the development of this promising program.”

Tern recently reported interim clinical data from the first six participants in its ongoing Phase 1/2 study of TTX-381. Results demonstrated a favorable safety profile, sustained and dose-dependent increases in TPP1 transgene expression, stabilized or improved photoreceptor integrity in all treated eyes, and early signals of stabilized or improved functional vision. These data formed the basis of Tern’s RMAT application to the FDA.

“RMAT designation provides strong validation of our approach to treating the rapid vision loss experienced by children with CLN2 and an opportunity to move even more quickly toward fulfilling our commitment to the CLN2 community,” said Christina Ohnsman, M.D., Chief Medical Officer of Tern.

RMAT designation is granted by the FDA to regenerative medicine therapies being developed to treat, modify, reverse, or cure serious or life-threatening diseases or conditions. To qualify, therapies must demonstrate preliminary clinical evidence of the potential to address the unmet medical needs for such diseases. Investigational therapies that receive RMAT designation are eligible to receive intensive guidance from the FDA as well as other actions to expedite development and review, including discussions about potential surrogate or intermediate endpoints and pathways to accelerated approval.

TTX-381 previously received Fast Track, Rare Pediatric Disease, and Orphan Drug Designations from the FDA.

Tern Therapeutics Receives US FDA Fast Track Designation for TTX-381 Gene Therapy for the Treatment of the Ocular Manifestations of CLN2 Disease

• Designation to expedite development of lead program TTX-381.

• First-in-human clinical trial to evaluate TTX-381 is active and recruiting patients

Tern Therapeutics, LLC (“Tern”), a biotechnology company developing transformative one-time gene therapies for rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to TTX-381. TTX-381 is a novel one-time gene therapy product being developed for the treatment of the ocular manifestations of CLN2 disease, a form of Batten disease.

“We are pleased the FDA has granted Fast Track designation to TTX-381, recognizing its potential to transform the lives of patients with CLN2 disease,” said Alex Bailey, Ph.D., Chief Executive Officer of Tern. “This marks an important milestone for Tern and reinforces the promise of TTX-381 to address the rapid, relentless loss of vision caused by CLN2 disease. With this designation, we look forward to working closely with the FDA to accelerate development and bring this much-needed therapy to patients as quickly as possible.”

The FDA’s Fast Track program is designed to help drugs reach patients sooner by expediting the development and regulatory review of therapies that address serious conditions with unmet medical needs. This designation facilitates increased interactions with the FDA during the clinical development process, as well as ensures eligibility for rolling review, priority review, and accelerated approval. TTX-381 previously received rare pediatric disease and orphan drug designations from the FDA.

Tern Therapeutics Issues CLN2 Batten Community Letter

Dear CLN2 Batten Community, We are pleased to share updates on Tern Therapeutics' progress with our clinical trials for TTX-381 and TTX-181, which are investigational gene therapies being developed for the treatment of CLN2 Batten disease. These therapies aim to address both the vision loss and neurological symptoms.

Although we are a new company, we were part of the team that originally developed these CLN2 Batten programs, and we are deeply grateful to our former colleagues who helped carry this important work forward, allowing us to continue the progress.

We are excited to share key milestones and positive data from the clinical trials which were presented at the 21st Annual WORLDSymposiumᵀᴹ in San Diego, CA. For more information on this news, here is a link to the press release: Tern Therapeutics Advances Pipeline and Presents Positive Clinical Data for TTX-381 and TTX-181 Gene Therapies for CLN2 Batten Disease at 21st Annual WORLDSymposiumᵀᴹ

Completion of Enrollment and Expansion for TTX-381 Trial: The Phase I/II clinical trial of TTX-381, which aims to treat vision loss associated with CLN2 Batten disease, has completed enrollment of Cohort 2, and selected the dose level for an expansion cohort. The trial is actively recruiting participants at Great Ormond Street Hospital in the United Kingdom.

Positive Clinical Data for TTX-381: Interim data from the trial show a favorable safety profile, increased TPP1 levels in treated eyes, and improvements in vision, with stabilization or improvement in the photoreceptor integrity of 100% of treated eyes. We have also observed promising functional vision outcomes.

Two-Year Data for TTX-181: A single patient study of TTX-181, which targets the neurological symptoms of CLN2 Batten disease, shows increases in TPP1 levels in the fluid surrounding the brain (cerebrospinal fluid, or CSF) through day 477 post-administration. This investigational gene therapy has also resulted in improvements in seizure control, stabilization of language and fine motor skills and allowed the patient to discontinue enzyme replacement therapy (ERT). Additional data at timepoints through 24 months post-administration are pending.

U.S. FDA Clearances: We are excited to announce that the U.S. Food and Drug Administration (FDA) has granted Investigational New Drug (IND) clearances for both TTX-381 and TTX-181, enabling us to continue developing these investigational gene therapies.

We remain committed to advancing both TTX-381 and TTX-181 through clinical trials, and we are encouraged by the progress made thus far. Our next steps include continuing to gather data to better understand the long-term effects of these therapies and working closely with regulatory agencies to bring these potential treatments to additional clinical trials.

We understand how important it is to have options for families living with CLN2 Batten disease, and we are focused on moving forward with urgency to provide meaningful therapies. We will continue to share updates with the Batten patient advocacy groups as they become available. Thank you for your trust and partnership in this journey. Should you wish to contact us, please email patientadvocacy@terntx.com.

Warm regards,
Tern Therapeutics

Questions you may have about TTX-381 and TTX-181 for CLN2 Batten disease.

What is TTX-381 and what does it do?
TTX-381 is a one-time investigational gene therapy designed to deliver a working copy of the TPP1 gene directly to the retina, which is essential for maintaining vision in children with CLN2 Batten disease. It aims to slow or even stop vision loss that occurs despite other treatments.

How is TTX-381 administered?
TTX-381 is administered as a one-time injection directly into the eye (subretinal administration). The goal is to preserve or restore photoreceptor health and vision in affected individuals.

What have the results been so far for TTX-381?
Early results from the trial are encouraging. All treated eyes have shown improvements or stabilization of photoreceptor integrity, and preliminary data suggest that functional vision may be either maintained or improved. The therapy has been well tolerated, with no serious side effects.

What is TTX-181 and how is it different from TTX-381?
TTX-181 is another one-time gene therapy that targets the neurological aspects of CLN2 Batten disease and is designed to deliver a working copy of the TPP1 gene to the central nervous system (CNS). Unlike TTX-381, which focuses on vision loss, TTX-181 addresses the disease's effects on the brain.

How has TTX-181 performed in clinical trials?
The results from the one-patient, investigator-initiated study of TTX-181 have been positive. The therapy was well tolerated, and it showed benefits in terms of seizure control, developmental stabilization, and allowed the discontinuation of enzyme replacement therapy (ERT) in a five-year-old patient. We are continuing to monitor the patient’s progress for further data.

How will these therapies help children living with CLN2 Batten disease?
Both TTX-381 and TTX-181 hold the potential to address two of the most urgent aspects of CLN2 Batten disease—vision loss and neurological degeneration. By targeting these core issues, these therapies could improve quality of life and slow disease progression for children and adults with CLN2 Batten disease.

What is an Investigational New Drug (IND) clearance?
An IND application is submitted to the U.S. Food and Drug Administration (FDA) by a Sponsor of a clinical trial to ask for permission to start the trial. The FDA reviews the application, which includes discovery, research results, the proposed clinical trial design, and product manufacturing to determine if the FDA believes the clinical trial is safe to start in humans.

Tern Therapeutics Advances Pipeline and Presents Positive Clinical Data for TTX-381 and TTX-181 Gene Therapies for CLN2 Batten Disease at 21st Annual WORLDSymposiumᵀᴹ

• Completed enrollment of Cohort 2 and selected dose level for an expansion cohort in the Phase 1/2 clinical trial of TTX-381, a potential one-time AAV gene therapy for the treatment of vision loss associated with CLN2 Batten disease. The trial is active and recruiting participants at Great Ormond Street Hospital (GOSH) in the United Kingdom.

• US FDA granted IND clearances for both its lead program, TTX-381, as well as for TTX-181, a potential one-time AAV gene therapy for the CNS manifestations of CLN2 Batten disease.

• Interim data from the clinical trial evaluating subretinal administration of TTX-381 show a favorable safety profile, rapid and sustained dose-dependent increases in tripeptidyl peptidase 1 (TPP1) transgene expression, stabilization or improvement of photoreceptor integrity in 100% of treated eyes, and promising changes in functional vision.

• Two-year data from a single patient investigator-initiated study show that intracisternal TTX-181 was welltolerated, achieved durable increases in TPP1 transgene expression that correlated with improvements in multiple clinically meaningful measures of efficacy, and allowed discontinuation of enzyme replacement therapy (ERT).

Tern Therapeutics, LLC (“Tern”), a biotechnology company developing transformative one-time gene therapies for rare diseases, reported the achievement of key development milestones for its programs TTX-381 and TTX-181, as well as presented positive clinical data relating to the safety and efficacy of both programs on February 7, 2025 at the 21st Annual WORLDSymposium™ in San Diego, California. TTX-381 and TTX-181 are novel one-time gene therapy products being developed for the treatment of the ocular and central nervous system (CNS) manifestations of CLN2 disease, a form of Batten disease.

Interim clinical data (n=6) from the ongoing Phase 1/2 clinical study evaluating TTX-381 at GOSH were presented by Christina Ohnsman, M.D., Chief Medical Officer of Tern. Physician investigators from the Hospital de Clinicas in Porto Alegre, Brazil presented two-year follow-up data from a single-patient, investigator-initiated study of TTX-181 administered to a five-year-old child.

"We are encouraged and energized by the TTX-381 clinical data showing photoreceptor preservation in the treated eyes of 100% of participants. This demonstrates the potential of TTX-381 as a one-time gene therapy to address the urgent unmet medical need of rapidly progressive vision loss caused by CLN2 disease. We are excited to report continued progress in the TTX-381 clinical trial," said Ohnsman.

“Intracisternal TTX-181 has had a very positive impact on our patient’s quality of life, with better seizure control, developmental stabilization, improved ability to communicate, and discontinuation of enzyme replacement therapy. However, some aspects of CLN2 that impact developmental skills were not addressed by TTX-181, especially vision loss,” said Carolina Fischinger Moura de Souza, MD, PhD, principal investigator. Roberto Giugliani, MD, PhD, who presented the data at the conference, added, “These results support initiation of a clinical trial to further explore safety, efficacy, dose level, and optimal age of administration for TTX-181.”

Program updates

Tern reported the completion of enrollment of Cohort 1 (n=3) and Cohort 2 (n=3) in the ongoing Phase 1/2 human clinical trial of TTX-381. Dose level 1 (2x1010 genome copies (GC)/eye) has subsequently been selected for an expansion cohort, and the trial is ongoing at GOSH in the United Kingdom. Tern also announced that it has received clearances from the United States Food and Drug Administration (FDA) for their Investigational New Drug (IND) applications for both TTX-381, its lead program, and TTX-181.

“We are thrilled with the progress we have made advancing our therapeutic pipeline. The opening of the INDs for TTX381 and TTX-181 represents a significant expansion of Tern’s capabilities, as well as provides us with an increased ability to collaborate with the FDA on the continued development of these promising programs” said Alex Bailey, PhD, Chief Executive Office of Tern.

Interim Data from TTX-381 Phase 1/2 Clinical Trial

Safety and Tolerability
As of the data cut-off on December 6, 2024, TTX-381 has been well tolerated at Dose Level 1 (2.0x1010 GC/eye; n=3) and Dose Level 2 (6.0x1010 GC/eye; n=3) with no serious adverse events (SAEs) related to the drug or administration procedure. Time of post-administration follow-up includes a minimum of six months for all participants and one year for participants in Cohort 1.

TPP1 Concentration in Aqueous Humor (AH)
In CLN2 Batten disease, TPP1 deficiency results in lysosomal accumulation of storage material and degeneration of nerve cells, particularly in the brain and retina. At baseline, all participants had either undetectable or trace concentrations of TPP1 in AH of both eyes. At day 90 following the administration of TTX-381, the treated eyes in 100% of participants (6/6) demonstrated dose-dependent increases in TPP1 expression compared with baseline, with 5 of 6 approximating or exceeding mean TPP1 concentrations of non-CLN2 eyes. Untreated eyes continued to have undetectable or trace concentrations of TPP1.

Anatomic Data from SD-OCT Imaging
Natural history data demonstrate that rapid photoreceptor degeneration in children with CLN2 is strikingly symmetrical in both eyes and first detectable in the ellipsoid zone (EZ). Areas with loss of the EZ as measured with SD-OCT directly correlate with areas of vision loss. Following administration of TTX-381, photoreceptor preservation as measured by stabilization or improvement in the area of EZ loss was observed in 6 of 6 participants, in contrast to progressive retinal degeneration in their untreated eyes. Differences in anatomic changes between treated and untreated eyes were observed as early as three months.

Functional Vision
Preliminary functional vision data suggest maintenance or improvement in visual skills in participants with the longest follow-up data available. These functional vision data, observed on a modified version of the Mullen Scales of Early Learning Visual Reception subscale, are consistent with stable to improved photoreceptor integrity observed on SD-OCT in treated eyes and with parental reports of maintained visual skills.

Data from TTX-181 Investigator-Initiated Study

Safety and Tolerability
As of the data cut-off on December 26, 2024, TTX-181 at a dose level of 1.25 x 1011 GC/gram of brain mass was well tolerated through two years post-administration with the patient experiencing no SAEs related to the drug or administration procedure.

TPP1 Concentration in cerebrospinal fluid (CSF)
TPP1 concentration was measured in CSF samples collected prior to administration of TTX-181 and at 12 timepoints through day 477 post-administration. Each sample was collected at least 19 days following infusion of ERT. Measurements showed a rapid and sustained 27- to 55-fold increase in CSF TPP1 compared with baseline through day 477 (last time point available). Additional data at timepoints through 24 months post-administration are pending.

Seizure Frequency, anti-epileptic medication use, and discontinuation of enzyme replacement therapy (ERT)
The monthly frequency of seizure events decreased by 90% after administration of TTX-181 in comparison with the frequency of seizures pre-administration and remained stable through two years. Two of four anti-epileptic medications were discontinued within six months. In addition, under the direction of the physician, intervals between ERT infusions were lengthened following administration of TTX-181, until ERT was ultimately discontinued at 16 months postadministration of TTX-181.

Neurodevelopment Measures
Stabilization or a small increase in age equivalent fine motor, receptive and expressive language skills were observed at two years post-administration of TTX-181, as compared with baseline on the Mullen Scales of Early Learning. Gross motor skills declined over the two years on this measure.

Tern Therapeutics Launches with $15 Million Financing and Pipeline in CLN2 Batten Disease

• Acquisition of programs from REGENXBIO Inc. form initial therapeutic pipeline

• Lead candidate is TTX-381, a novel, one-time investigational gene therapy for the treatment of the ocular manifestations of CLN2 Batten disease

• $15 million funding round to accelerate ongoing clinical testing of TTX-381 and advance pipeline

Tern Therapeutics, LLC (“Tern”), a biotechnology company developing transformative one-time gene therapies for rare diseases, today announced its launch and closing of a $15 million financing. Concurrently, Tern also announced that it has entered into a global licensing agreement with REGENXBIO Inc. ("REGENXBIO") for RGX-381 and RGX-181 (now designated TTX-381 and 181, respectively) to form its initial therapeutic pipeline. TTX-381 and TTX-181 are novel one-time gene therapy products being developed for the treatment of the ocular and central nervous system (CNS) manifestations CLN2 disease, a form of Batten disease. The financing will be used to accelerate the ongoing clinical testing of the company’s lead candidate, TTX-381, and advance its pipeline.

Tern management has deep expertise in the life sciences industry, specifically in gene therapy and ophthalmology. Founders Alex M. Bailey, PhD, Chief Executive Officer, and Christina Ohnsman, MD, Chief Medical Officer, were integral leaders in the CLN2 Batten disease programs at REGENXBIO. Bailey was previously Head of Early Program and Portfolio Development at REGENXBIO and held a leadership role at the Center for Biologics Evaluation and Research (CBER) within the United States Food & Drug Administration (FDA). Ohnsman was Executive Director of Clinical Development at REGENXBIO and previously served on the faculty of Wills Eye Hospital in Philadelphia and provided strategic consulting to ophthalmic biopharma, gene therapy, and device companies. Tern founder and Chief Financial and Administrative Officer Matthew Rosini was Head of Strategic Initiatives at REGENXBIO and previously was a Partner at FoxKiser LLP, a law firm providing strategic consulting and legal advice to life sciences clients.

“We’re driven to deliver transformative treatments to patients living with rare diseases and are excited to continue the work we started at REGENXBIO. No one knows these programs better than the team we’ve assembled at Tern, and we deeply appreciate the confidence and trust that REGENXBIO and the patient community have placed in us to lead the next phase of development of these promising investigational therapies,” said Bailey.

“We founded Tern Therapeutics out of a deep personal commitment to serving patients with high unmet needs. Children with CLN2 and their families have long been waiting for treatment with gene therapy. This financing will allow us to advance our lead candidate, TTX-381, through the clinic as rapidly as possible,” said Ohnsman.

The investment was led by ATW Partners and biotech investor Steve Oliveira, head of Nemean Asset Management. “We are thrilled to partner with the talented team at Tern and look forward to making a meaningful difference in the lives of CLN2 patients,” said Oliveira. Kerry Propper, Founder and Managing Partner of ATW Partners, added, “We are especially excited to support Tern’s mission to work towards a cure for blindness in children with CLN2, a devastating aspect of the disease.”

Patient communities are central to Tern’s approach to the development of investigational therapies, including partnerships with the Batten Disease Family Association (BDFA); Batten Disease Support, Research, & Advocacy (BDSRA); BDSRA Australia; and other patient advocacy organizations.

BDFA CEO Liz Brownnutt said, “As the only patient organisation in the UK for families affected by Batten disease, we understand the profound and long-lasting impact that Batten disease has on patients and their loved ones, and we are acutely aware of the urgent need for effective treatments to alleviate the suffering caused by this devastating condition. We are therefore delighted that Tern Therapeutics plans to advance the CLN2 programs and we look forward to the further development of the ocular trial here in the UK. We believe that with their unique qualifications and capabilities, this team has the potential to extend hope for patients and families living with CLN2 Batten disease.” BDSRA President and CEO Amy Fenton Parker said, “This development is incredibly encouraging for our CLN2 community. The transition of both gene therapy programs to the Tern Therapeutics team, who are already so familiar with the programs and connected to our CLN2 community, is invaluable for the seamless continuity and advancement of this clinical research.” Ineka Whiteman, PhD, Head of Research & Medical Affairs for BDSRA USA and BDSRA Australia, added, “We cannot conceive of a more qualified team for these programs and BDSRA Foundation continues to offer its support and collaboration to Tern Therapeutics to ensure these programs continue advancing as swiftly and effectively as possible.”

TTX-381 is an investigational one-time AAV gene therapy designed to deliver a working copy of the TPP1 gene directly to the retina, potentially providing a durable source of TPP1 activity intended to maintain the health of the retina and address vision loss in people with CLN2 disease. The safety and tolerability of TTX-381, as well as its effect on retinal anatomic and functional outcomes, is being evaluated in a first-in-human, open-label, dose escalation Phase I/II clinical trial at Great Ormond Street Hospital in London, UK.

TTX-181 is an investigational one-time AAV gene therapy designed to deliver a working copy of the TPP1 gene directly to the central nervous system (CNS), potentially providing sustained levels of TPP1 intended to prevent worsening of neurological degeneration in people with CLN2 disease. In late 2022, physician investigators at the Hospital de Clinicas in Porto Alegre, Brazil dosed a child with CLN2 Batten disease with TTX-181 in a single-patient, investigator-initiated study.