Programmable Medicine Presents Preclinical Data Supporting Myeloid-Directed JAK-Dendranib Development for Rheumatoid Arthritis
Programmable Medicine (PMED), a biotechnology company developing targeted nanomedicine approaches for inflammatory diseases, announced that it will present new preclinical findings supporting the development of its investigational JAK-dendranib program at ACR Convergence 2026. The research highlights a new class of myeloid-directed Janus kinase (JAK) inhibitors designed to provide effective control of rheumatoid arthritis (RA) while potentially improving the safety profile associated with conventional JAK inhibitor treatments.
The company’s development strategy combines JAK inhibition, an established therapeutic approach for controlling inflammatory signaling, with the selective delivery capabilities of its proprietary hydroxyl dendrimer technology platform. Through this combination, Programmable Medicine aims to direct therapeutic activity toward activated myeloid cells, which play an important role in the inflammatory processes responsible for joint damage in rheumatoid arthritis.
The JAK-dendranib program is designed to address an important challenge in treating autoimmune and inflammatory diseases: achieving sufficient disease control without unnecessarily affecting other components of the immune system. Although conventional JAK inhibitors have demonstrated clinical benefits in inflammatory conditions, concerns about their safety, including infection risks, have highlighted the need for alternative approaches that could offer more selective therapeutic activity.
Jeffrey L. Cleland, PhD, Chief Executive Officer of Programmable Medicine, said the company’s objective is to deliver the disease-control benefits associated with JAK inhibition while developing an improved safety profile compared with conventional treatments such as baricitinib.
He explained that directing JAK inhibition toward activated myeloid cells could help preserve adaptive immune function while potentially reducing the infection burden associated with broader immune pathway inhibition. The company’s research is focused on determining whether this targeted delivery strategy can maintain therapeutic effectiveness while limiting unwanted effects on other immune cell populations.
Presentation at ACR Convergence 2026
Programmable Medicine will share its findings through a scientific poster presentation at ACR Convergence 2026, the annual meeting of the American College of Rheumatology. The presentation will discuss the company’s research into myeloid-directed JAK-inhibiting nanomedicine and its potential application in rheumatoid arthritis.
The poster will provide details of preclinical investigations evaluating the ability of hydroxyl dendrimer-based JAK inhibitors to target inflammatory cells and improve disease outcomes in experimental models of arthritis.
Poster Presentation Details
- Presentation Title: Targeting Rheumatoid Arthritis with Myeloid-Directed JAK-Inhibiting Nanomedicine
- Abstract Number: 2028
- Submission Number: 2455902
- Session: Poster Session C, Rheumatoid Arthritis – Translational Models and Mechanisms
- Date: Tuesday, November 10, 2026
- Presentation Time: 10:30 AM–12:30 PM
- Presenter: Madhuri Chattopadhyay, PhD, Senior Scientist, Programmable Medicine
- Conference: ACR Convergence 2026
The published abstract is available through the ACR Abstracts platform.
The presentation will highlight the scientific rationale behind the JAK-dendranib platform, including the role of activated myeloid cells in rheumatoid arthritis, the selective uptake properties of hydroxyl dendrimers, and the therapeutic effects observed in preclinical studies.
Addressing Unmet Needs in Rheumatoid Arthritis Treatment
Rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation of the joints. The condition develops when the immune system mistakenly attacks healthy tissues, particularly the synovial lining surrounding the joints. Persistent inflammation can gradually damage cartilage and underlying bone, resulting in pain, swelling, stiffness, and reduced physical function.
The disease can affect multiple joints and may progress over time if inflammation is not adequately controlled. Patients may experience difficulties performing everyday activities, including walking, dressing, handling objects, and completing routine household or professional responsibilities.
Several immune cell populations contribute to the development and progression of rheumatoid arthritis. Among these, myeloid cells are important drivers of inflammatory activity within affected joints. These cells can migrate into inflamed tissues and contribute to the release of inflammatory mediators that sustain disease activity and promote tissue destruction.
Activated myeloid cells can therefore represent an important therapeutic target for controlling inflammation and limiting joint damage.
Current rheumatoid arthritis treatment strategies include conventional disease-modifying antirheumatic drugs, biologic therapies, and targeted synthetic treatments. JAK inhibitors are among the targeted treatment options used to interfere with intracellular signaling pathways involved in inflammation and immune responses.
However, JAK signaling is involved in several biological processes across different immune cell populations. Conventional JAK inhibitors can therefore influence multiple immune functions, which may contribute to safety considerations, including an increased risk of infections in certain patients.
Programmable Medicine is developing its JAK-dendranib candidates to explore whether more selective delivery of JAK inhibition can help address these challenges.
By directing therapeutic compounds toward activated myeloid cells, the company aims to reduce inflammatory activity in affected tissues while preserving important functions of the adaptive immune system.
Hydroxyl Dendrimer Platform Enables Targeted Drug Delivery
The foundation of Programmable Medicine’s JAK-dendranib development program is its proprietary hydroxyl dendrimer technology platform.
Dendrimers are highly structured, branched macromolecules that can be engineered for specific drug-delivery applications. Their molecular architecture provides opportunities to incorporate therapeutic compounds and influence how they interact with biological systems.
Programmable Medicine is using hydroxyl dendrimers to develop targeted nanomedicine candidates designed to take advantage of the selective uptake properties of particular immune cell populations.
According to the company, hydroxyl dendrimers are selectively taken up by activated myeloid cells in arthritic joints in mice. This characteristic provides the scientific basis for investigating the platform as a delivery mechanism for JAK inhibitors.
The company’s JAK-dendranib candidates combine this targeting capability with the established pharmacological activity of JAK inhibition.
The approach is intended to concentrate therapeutic activity in the cells contributing to inflammatory disease processes rather than exposing multiple immune cell populations to the same level of pathway inhibition.
This distinction could be important for inflammatory disease treatment because the immune system relies on several interconnected pathways to maintain normal protective functions.
By targeting activated myeloid cells, Programmable Medicine hopes to achieve a more focused anti-inflammatory effect while potentially reducing the impact on adaptive immunity.
The company believes this strategy could provide a differentiated approach to treating rheumatoid arthritis and potentially other inflammatory conditions where myeloid cells contribute significantly to disease progression.
Preclinical Study Demonstrates Improvements in Arthritis Disease Scores
Programmable Medicine evaluated three JAK-dendranib candidates in a 14-day preclinical study using a mouse model of rheumatoid arthritis.
The study was designed to assess the therapeutic effects of the investigational compounds on arthritis disease activity and determine whether targeted JAK inhibition could reduce inflammation and joint deterioration.
According to the company, all three JAK-dendranib candidates significantly improved arthritis disease scores during the study period.
The observed efficacy was comparable to baricitinib, an established JAK inhibitor used in the treatment of inflammatory conditions, including rheumatoid arthritis.
This comparison is an important component of the company’s preclinical research because it provides an indication of the therapeutic activity that may be achieved through the dendrimer-based delivery approach.
Arthritis disease scores are commonly used in experimental models to evaluate the severity of inflammation and disease progression. Improvements in these measurements can provide evidence that a treatment is reducing inflammatory activity.
The findings suggest that the JAK-dendranib candidates were able to produce meaningful anti-arthritis effects in the experimental model.
Importantly, the research also examined the effects of treatment on joint tissue structure, providing additional information beyond changes in overall arthritis disease scores.
Although these findings are encouraging, the results are based on an animal model and do not establish clinical efficacy in humans. Additional research will be required to determine whether similar therapeutic effects can be achieved in patients with rheumatoid arthritis.
Lead Candidate Reduces Inflammation and Joint Tissue Damage
In addition to improvements in arthritis disease scores, microscopic examination of joint tissues revealed further evidence supporting the JAK-dendranib development program.
According to Programmable Medicine, histological evaluation showed that a lead candidate significantly reduced inflammation and joint damage.
The observed improvements included reductions in cartilage damage and bone resorption.
Cartilage is an essential component of joint structure, providing a smooth surface that allows bones to move against one another with minimal friction. In rheumatoid arthritis, persistent inflammation can damage cartilage, gradually affecting joint movement and physical function.
Bone resorption is another important feature of progressive rheumatoid arthritis. Inflammatory processes can activate cells responsible for breaking down bone tissue, contributing to erosions and structural damage.
These changes can result in long-term joint deformity, pain, and disability.
The ability of the lead JAK-dendranib candidate to reduce these tissue changes in the preclinical model provides additional support for its potential therapeutic activity.
The combination of improved arthritis scores and reduced structural damage suggests that the investigational compounds may influence both inflammatory disease activity and tissue-level consequences of the condition.
For Programmable Medicine, these results represent preclinical proof of concept for its myeloid-directed JAK inhibition strategy and support further investigation of the platform.
Safety Considerations and Development Rationale
An important objective of the JAK-dendranib program is to investigate whether targeted delivery can improve the safety profile associated with conventional JAK inhibition.
S. Sakura Minami, PhD, Vice President of Translational Medicine and Nonclinical Development at Programmable Medicine, said the observed efficacy findings, together with the hydroxyl dendrimer technology platform’s previous safety experience, support continued development of the program.
Minami also highlighted two characteristics of the hydroxyl dendrimer platform: rapid renal clearance and the lack of liver metabolism.
These properties are considered relevant to the company’s development strategy because they may influence how the delivery platform is processed and eliminated by the body.
Rapid renal clearance refers to the removal of compounds through the kidneys, while limited reliance on liver metabolism may reduce the need for certain metabolic processing pathways.
According to the company, these characteristics, combined with prior animal studies and clinical trial experience involving the hydroxyl dendrimer technology platform, strengthen the rationale for investigating its application in targeted inflammatory disease treatment.
The broader objective is to develop a therapeutic approach that maintains disease control while potentially reducing unwanted systemic immune effects.
However, the safety and pharmacological characteristics of each investigational JAK-dendranib candidate will need to be established through appropriate studies. Preclinical findings and prior platform experience do not independently establish the safety of the new drug candidates in humans.
Further nonclinical and clinical research will be necessary to determine whether the targeted approach can deliver the intended safety advantages.
Programmable Medicine Seeks Development Partners
Alongside its scientific and preclinical development activities, Programmable Medicine is seeking strategic partners to help advance its JAK-dendranib program toward clinical development.
Mukul Agarwal, Chief Business Officer of Programmable Medicine, said the company is interested in collaborating with partners to move the new class of myeloid-directed JAK inhibitors into clinical studies.
The partnership strategy reflects the company’s broader ambition to develop treatments for inflammatory diseases that combine effective disease control with improved safety characteristics.
Strategic collaborations could support several aspects of the program, including further research, drug development, manufacturing, clinical evaluation, and potential commercialization.
For biotechnology companies developing novel drug-delivery platforms, partnerships can provide access to additional scientific expertise, development resources, and industry capabilities needed to advance investigational therapies.
Programmable Medicine believes its targeted nanomedicine approach could expand treatment possibilities for patients whose care is affected by the limitations or safety considerations associated with existing therapies.
The company is particularly interested in developing therapeutic options that address inflammatory disease mechanisms while minimizing unnecessary effects on healthy immune functions.
Next Steps for the JAK-Dendranib Program
The preclinical findings presented at ACR Convergence 2026 represent an important milestone in Programmable Medicine’s efforts to develop myeloid-directed JAK inhibitors.
The company’s research has demonstrated that three investigational candidates significantly improved arthritis disease scores in a mouse model, with efficacy comparable to baricitinib. In addition, microscopic analysis showed that a lead candidate reduced inflammation, cartilage damage, and bone resorption.
Together, these findings support continued investigation of the hydroxyl dendrimer platform as a potential delivery technology for targeted JAK inhibition.
The next stages of development will need to establish the candidates’ pharmacological properties, safety characteristics, and potential clinical benefits. Further studies will also be important in determining whether myeloid-directed delivery can provide meaningful advantages over conventional JAK inhibitor approaches.
If supported by additional research, the strategy could offer a differentiated approach to managing rheumatoid arthritis and other inflammatory diseases involving activated myeloid cells.
Programmable Medicine is continuing to explore opportunities to advance the program through strategic partnerships and discussions with potential collaborators.
The company has invited interested organizations and industry representatives to schedule meetings during ACR Convergence 2026 or the J.P. Morgan Healthcare Conference in January 2027.
For partnership discussions and meeting requests, interested parties can contact bd@pmed.com.
Through its JAK-dendranib program, Programmable Medicine aims to combine established inflammatory pathway inhibition with targeted nanomedicine delivery, potentially creating a new treatment approach focused on balancing disease control and immune system safety.
About JAK-Dendranibs
JAK-dendranibs are investigational hydroxyl dendrimer therapeutics in which proprietary Janus kinase (JAK) inhibitors are conjugated to hydroxyl dendrimers. The program combines myeloid- selective uptake with JAK inhibition to develop disease-modifying antirheumatic drug candidates. Preservation of adaptive immune function and reduced infection burden remain potential benefits to be evaluated.
About Programmable Medicine
Programmable Medicine (PMED) is a clinical-stage company developing hydroxyl dendrimer therapeutics (HDTs) that selectively deliver medicines to activated inflammatory cells, including macrophages and microglia. By targeting cell state rather than cell type alone, HDTs are designed to reprogram inflammatory cells while preserving healthy tissue and expanding the therapeutic index.
HDTs have demonstrated a robust safety record across eight clinical trials—five Phase 1 and three Phase 2—in more than 100 patients, providing a foundation for advancing PMED’s pipeline across inflammatory diseases. For more information, visit www.pmed.com.