Alloplex Biotherapeutics is pioneering a novel approach to cancer immunotherapy through its proprietary ENLIS immune cell training platform. This innovative platform forms the foundation for our lead therapeutic candidate, SUPLEXA, a non-engineered autologous cellular therapy that has demonstrated promising clinical activity and a favorable safety profile in a completed Phase 1 trial.
We invite scientists and clinicians to explore the unique science and significant potential of our approach.
The cornerstone of our approach is the ENLIST (ENgineered Leukocyte Immune STimulator) immune cell training platform. Recognizing the potential of activating multiple immune pathways for anti-tumor activity, Alloplex's scientific founder, Dr. Frank Borriello, developed this patented platform.
SUPLEXA therapeutic cells are the result of this ENLIST-mediated training. They are a highly differentiated and non-engineered autologous cell population derived from the patient's own PBMCs. Unlike genetically modified cell therapies, SUPLEXA cells retain their naturally occurring receptors and are driven by physiologic signals. This approach may contribute to a more efficacious and safe therapy by preserving natural trafficking patterns and homeostatic mechanisms. Opinion leaders have indicated that safety is unlikely to be an issue. The absence of genetic alterations also bypasses potential safety concerns associated with DNA engineering techniques, such as tumorigenic mutations.
Generated without any genetic modification, relying on the natural activation of the patient's immune cells through physiological signals. This potentially contributes to the exceptional safety profile and preserves the natural complexity of the immune system. The absence of genetic alterations bypasses potential safety concerns associated with DNA engineering techniques, such as tumorigenic mutations.
Differentiated cell therapy comprised of highly-activated lymphoid cells with unique features. This enables a coordinated attack on tumors from independent directions. This allows for direct tumor lysis, antigen presentation, and amplification of the host anti-tumor response.
Demonstrates broad killing activity against various tumor cells while sparing normal, healthy cells, indicating tumor-specific targeting that appears independent of HLA. This suggests activity possibly against ubiquitous tumor-specific motifs, such as tumor cell stress antigens.
Significantly differs from PBMCs by lacking immunosuppressive cell types such as Tregs and myeloid-derived suppressor cells (MDSC) that might suppress the anti-tumor response.
Exhibits immunomodulatory effects in cancer patients, consistent with improved anti-tumor immune function. They can potentially alter the tumor microenvironment.
PBMCs are collected using a standard isolation procedure from a small, easily-collected sample of the patient's peripheral blood. No further cell selection is required — simply place them in a flask with standard expansion media, and the ENLIST reagents supply all the necessary signals in a fixed ratio to generate SUPLEXA cells.
The first-in-human Phase 1 clinical trial (SUPLEXA-101) in Australia has been successfully completed, achieving all study endpoints. This open-label, single-agent study assessed the safety, tolerability, and preliminary efficacy of SUPLEXA in 35 patients with various metastatic solid tumors who had exhausted all standard treatment options. The trial commenced in 2Q 2022.
An exceptional safety profile was observed with no drug-related serious adverse events (SAEs) identified across a wide dose range (3-20 doses of 2.5 billion cells per patient) and over 220 administered doses.
No related Dose Limiting Toxicities (DLTs) or injection site reactions were reported. This was consistent with preclinical animal data and the absence of genetically engineered receptors. As an autologous therapy, there was no theoretical possibility of graft vs host or host vs graft activity.
Analyses of longitudinal peripheral blood samples revealed marked pharmacodynamic changes favoring an anti-tumor immune response. This included dramatic decreases in myeloid-derived suppressor cells (MDSC) combined with increases in activated monocytes (specifically, activated classical monocytes - SIGLEC-1+).
Baseline immune cell characteristics showed higher levels of NK cells and lower levels of MDSCs in patients showing clinical benefit. Longitudinal plasma samples revealed modulation of cytokines impacting inflammatory cytokine (IL-6) and hematopoietic factor (cKit) networks.
While not a formal endpoint, patients reported improvements in their well-being, a reduction in pain, and improved symptom control, allowing them to resume normal activities. As Associate Professor Rohit Joshi, Principal Investigator of the trial, stated: "The fact that we can actually get a clinical response... with people getting back to normal life and excellent symptom control, is quite remarkable".
The positive outcomes from the Phase 1 trial were recognized when the SUPLEXA trial results were selected among the Top 100 presentations at the prestigious SITC 2024 annual meeting. This provides significant external validation from experts in the field. Opinion leaders described the approach as "very elegant" and "as good as it gets".
A crucial factor for scalability, accessibility, and commercial viability, the manufacturing process for SUPLEXA therapeutic cells is designed to be simple, robust, and reproducible.
Furthermore, SUPLEXA requires less than 50mL of whole blood to manufacture a sufficient number of doses for an entire course of therapy, compared to significant patient burdens (surgical procedures, apheresis, chemotherapy ablation) often associated with other cellular approaches.
While the initial focus of the ENLIST platform is the development of SUPLEXA for oncology, its underlying principle of retraining immunosuppressed immune cells holds broader potential. The ability of ENLIST to modulate immune cell activity suggests future applications. The platform's compatibility with various cell types and potential for allogeneic "off-the-shelf" therapies and integration with engineering methods further expands its possibilities.
Alloplex Biotherapeutics is actively seeking strategic partnerships with pharmaceutical companies and academic research institutions to further develop and explore the full potential of the ENLIST immune cell training platform as well as SUPLEXA, the first clinical stage PBMC-derived cellular therapy for treating malignancies to be generated using this platform. With multimodal features, SUPLEXA can complement and synergize with a number of other drug development efforts.
We see potential collaborations in areas such as:
Alloplex offers the no-risk option to independently test the ENLIST immune cell training platform for specific applications through an MTA agreement.
Scientists, clinicians and business development individuals interested in learning more or discussing potential collaborations are encouraged to contact us.
