Kenai Therapeutics Completes Enrollment in REPLACE Trial of iPSC-Derived Dopaminergic Neuron Therapy RNDP-001 in Parkinson's Disease

Kenai Therapeutics announced today the completion of enrollment in the REPLACE (Replacing Neurons Absent in Parkinson's with Cell-Derived Efficacious dopaminergic cells) phase 1b/2a clinical trial of RNDP-001, an allogeneic, off-the-shelf cell therapy composed of iPSC-derived dopaminergic neurons, in patients with idiopathic Parkinson's disease (PD).¹ The milestone represents the most advanced allogeneic iPSC-based neuron replacement program to complete phase 1b/2a enrollment in PD, advancing a decades-long effort to move beyond symptomatic management toward actual cellular restoration of the damaged dopaminergic circuitry that drives disease progression. The trial is part of a broader wave of regenerative medicine approaches that are reshaping how the field thinks about neurodegeneration as a potentially treatable, not just manageable, condition.

What is Parkinson's disease and why is neuronal replacement an attractive strategy?

PD is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in dopamine depletion in the striatum and the classic motor triad of bradykinesia, rigidity, and tremor.² The disease affects an estimated 10 million people worldwide, with incidence rising sharply with age — making it the second most common neurodegenerative disease globally after Alzheimer's disease.² While symptomatic therapies including levodopa, dopamine agonists, and deep brain stimulation can meaningfully improve motor function, they address downstream consequences of neuronal loss rather than the underlying pathology itself and are associated with diminishing benefit and increasing side effects over time.³

The concept of replacing lost dopaminergic neurons directly is not new — fetal tissue transplantation trials in the 1980s and 1990s demonstrated that transplanted dopaminergic neurons could survive, integrate, and provide sustained clinical benefit in some patients for up to 24 years post-transplant.⁴ However, ethical constraints, tissue availability, and donor variability limited the scalability of fetal cell approaches. iPSC technology has provided a path to an ethically acceptable, reproducible, and potentially scalable source of dopaminergic neurons — and the allogeneic format pursued by Kenai removes the need for autologous manufacturing, which is prohibitively time-intensive and expensive for a neurodegenerative disease where treatment urgency is high.

What is RNDP-001 and how does it work?

RNDP-001 is an allogeneic, off-the-shelf cell therapy product comprising iPSC-derived dopaminergic neuron progenitor cells manufactured from a standardized, banked iPSC master cell line.¹ The product is designed to be surgically transplanted into the putamen — the striatal target of the nigrostriatal dopaminergic pathway — where the transplanted cells are intended to mature into functional dopaminergic neurons, integrate into host circuitry, and restore dopamine release in the denervated striatum.

The allogeneic approach introduces immunological considerations not present in autologous programs — transplanted cells from a non-self donor may be subject to immune rejection — and Kenai's manufacturing and clinical strategy incorporates appropriate immunosuppression protocols to support graft survival during the engraftment period.¹ Preclinical data supporting RNDP-001's development have demonstrated cell survival, dopaminergic differentiation, and functional integration in animal models of PD, providing the biological rationale for clinical testing.¹ RNDP-001 has received FDA Fast Track designation, reflecting the agency's recognition of the program's potential to address a serious unmet need.¹

What is the REPLACE trial design?

The REPLACE trial (ClinicalTrials.gov: NCT06205394) is a Phase 1b/2a, open-label, multicenter, dose-escalation study evaluating the safety, tolerability, and preliminary efficacy of RNDP-001 in patients with idiopathic PD.¹ The trial is conducted at leading academic medical centers across the US, with partial funding from the California Institute for Regenerative Medicine (CIRM) — one of the most significant sources of state-based funding for cell and gene therapy development in the US — which has supported Kenai's program as part of its mission to accelerate regenerative medicine toward patients.¹

Primary endpoints include safety and tolerability; secondary endpoints include preliminary measures of motor function, quality of life, and neuroimaging assessments of dopaminergic function. Safety data and initial efficacy readouts are anticipated in 2027. As Yelena Ionova, a cell and gene therapy quality and manufacturing expert, noted in a recent BioPharm International interview on CGT manufacturing compliance: "Increased regulatory scrutiny across the cell and gene therapy sector is driving manufacturers to take a more proactive and data-driven approach to inspection readiness and quality oversight" — a compliance posture directly relevant to allogeneic iPSC programs navigating their first clinical milestones.

How does RNDP-001 fit in the broader iPSC dopaminergic cell therapy field?

Kenai's REPLACE trial is one of a small number of iPSC-based dopaminergic cell therapy programs advancing in the clinic globally. Parallel programs include autologous iPSC-derived dopaminergic progenitor transplantation studies at McLean Hospital (NCT06422208) and Massachusetts General Hospital (NCT06687837), both funded through NIH mechanisms and currently in phase 1 recruitment in the US, and a collaboration-based allogeneic program at Kyoto University in Japan that has demonstrated preliminary safety signals.⁵ The field is also watching early data from Bayer/AskBio's AAV2-GDNF gene therapy program, which takes a complementary neuroprotective rather than replacement approach.

Kenai's allogeneic, off-the-shelf format distinguishes RNDP-001 from autologous programs on scalability grounds — if safety and efficacy can be demonstrated in REPLACE, the manufacturing model is better positioned for broad commercial deployment than patient-specific autologous approaches.

"Completing enrollment in the REPLACE trial is a pivotal moment for Kenai and for the Parkinson's disease community," said Nick Manusos, chief executive officer of Kenai Therapeutics. "We are committed to developing a transformative therapy that not only alleviates the symptoms of Parkinson's disease but aims to restore the lost dopaminergic neurons that are at the root of the disease. This milestone brings us one step closer to potentially offering patients a new treatment paradigm."¹

References

1. Kenai Therapeutics Announces Completion of Enrollment in Phase 1b/2a REPLACE Trial of RNDP-001 in Idiopathic Parkinson's Disease. (2026 Jul 7). PR Newswire. https://www.prnewswire.com/news-releases/kenai-therapeutics-announces-completion-of-enrollment-in-phase-1b2a-replace-trial-of-rndp-001-in-idiopathic-parkinsons-disease-302818826.html
2. Poewe W, Seppi K, Tanner CM, et al. (2017 Mar 23). Parkinson disease. Nat Rev Dis Primers. https://pubmed.ncbi.nlm.nih.gov/28332488/
3. Wang F, Sun Z, Peng D, et al. (2023 Sep 7). Cell therapy for Parkinson's disease: a systematic review and meta-analysis. J Transl Med. https://pubmed.ncbi.nlm.nih.gov/37679754/
4. Li W, Englund E, Widner H, et al. (2016 Jun 7). Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain. Proc Natl Acad Sci USA. https://pubmed.ncbi.nlm.nih.gov/27140603/
5. Hiller BM, Marmion DJ, Thompson CA, et al. (2022 Apr 21). Optimizing maturity and dose of iPSC-derived dopamine progenitor cell therapy for Parkinson's disease. npj Regen Med. https://www.nature.com/articles/s41536-022-00221-y
6. A Study to Assess Safety and Efficacy of Surgical Implant of RNDP-001 in Patients With Idiopathic Parkinson's Disease. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT06205394