To render this idea commercially viable, we developed a reliable and robust manufacturing process which employs 50mls of patient whole blood, is manufactured under GMP conditions, resulting in multiple SUPLEXA therapeutic doses.
In the highly competitive space of oncology research and development, the specific field of cellular therapy and, more generally, immuno-oncology is booming. Today, we are witnessing unprecedented international investment in research designed to improve clinical outcomes in cancer through augmenting the antitumor activity of the patient’s own immune system.
Employing a novel approach to the challenge, Alloplex focused on creating SUPLEXA therapeutic cells, an individualized, non-engineered cellular therapy.
The oncology cellular therapy commercial landscape is currently (2023) comprised exclusively of several approved CAR-T products. Researchers are expanding on this early success by adding additional features to CAR-T cell constructs as well as exploring other cell types to engineer such as NK, γδ-T cells, macrophages, B cells, TILs and iNK cells.
Conversely, SUPLEXA therapeutic cells are comprised of many different cell types of both the innate and adaptive immune systems and each individually known to possess anti-tumor activity. It is an autologous therapy, created from a small amount of the patient’s peripheral blood coincubated with proprietary training cells, known as ENLIST cells.
The company has been undertaking exacting research on its original concept since 2016 when scientific founder Frank Borriello, MD, PhD developed the concept and registered the first patent for proprietary ENLIST cells.
Nonclinical research suggested SUPLEXA therapeutic cells would be well-tolerated and safe and this has now been borne out in the first in human clinical trial.
The first generation GMP manufacturing is well-established and recent improvement in processing have led to a second-generation process resulting in SUPLEXA cells with cytolytic activity in vitro augmented by approximately 10-fold.
The first in human clinical trials, which commenced in 2Q2022, are progressing well and are demonstrating excellent safety and tolerability and encouraging early signals of outcomes.
“The SUPLEXA approach has proven to be remarkably robust and versatile, yielding highly efficacious results in all preclinical experiments to date.
Furthermore, observations from our first-in-human studies have not only extended these preclinical safety and efficacy data but have also revealed an unanticipated immunomodulation beneficial to an anti-tumor response.”
In the large, dynamic and highly competitive field of cellular therapies, the ultimate goal is to deliver an efficacious and safe product that is well-tolerated.
Alloplex presents an opportunity to invest in a highly differentiated asset with exceptional promise. The proprietary ENLIST cell platform, by which SUPLEXA therapeutic cells are generated, offers multiple opportunities to broaden the pipeline and generate strategic partnerships. Moreover, the combination of IP and trade secrets ensures that a first-mover advantage is maximized.
SUPLEXA shows potential as a single agent against multiple tumor cell types or in combination with any immune cell sparing therapies. See Preclinical and Clinical data below.
While Alloplex has opted to make our first-generation product autologous for a variety of theoretical and strategic reasons, there is potential to develop a future allogeneic administration, off-the-shelf therapy and even integrate an engineering step, should one prove to be particularly advantageous.
Alloplex is confident that there is much to recommend its technology platform and welcomes discussions with potential investors with a commitment to cellular therapies.
Note: If you are interested in contacting Alloplex, please complete the form on this page instead.
Alloplex is a privately held company with operations in Boston, USA and a wholly owned subsidiary in Melbourne, Australia.
Alloplex was founded by Dr. Borriello, a Harvard-trained immunologist with more than 20 years in the pharmaceutical industry. He has served in diverse roles ranging from clinical development to external innovation assessment and business development.
He heads a small and nimble leadership team at Alloplex whose members bring broad and complementary skill sets that span immunology and analytical science, pharmaceutical development, clinical and regulatory expertise, and business development.
Dr. Borriello is joined by:
Drs. Borriello and Lederer, the company’s Chief Scientific Officer, have presented at key cancer conferences and meetings on the unique science and mechanism of action of the proprietary ENLIST training cells and the resulting SUPLEXA therapeutic cells.
Alloplex has developed SUPLEXA therapy; a non-engineered autologous PBMC-derived cellular therapy based on a novel concept that relies on the foundational observation that many known immune pathways possess some degree of anti-tumor activity.
In the process, Alloplex has identified several instances of unexpected synergistic activity in which simultaneous activation of distinct pathways led to a stronger than expected expansion of cells with anti-tumor activity.
These ENLIST training cells serve as a platform that can be varied to engage and activate various PBMC subsets with the near-term objective of enhancing the anti-tumor activity. The resulting activated cells are called SUPLEXA therapeutic cells and are comprised of NK, NKT, γδ-T cells and αβ-T cells of both CD8 and CD4 phenotypes, effectively representing a cross section of both the innate and adaptive immune systems. These cell types have been shown by others to individually possess anti-tumor activity. In contrast, SUPLEXA therapeutic cells lack immunosuppressive cell types such as Tregs and myeloid-derived stromal cells (MDSC) that might suppress the anti-tumor response.
The ENLIST cell platform by which SUPLEXA therapeutic cells are generated offers multiple opportunities to broaden the pipeline and generate strategic partnerships.
SUPLEXA cells are broadly cytolytic against a variety of tumor cells but do not target normal naïve or activated immune cells, confirming that the targeting phenomenon is tumor-specific. The emerging hypothesis is that SUPLEXA cells mount a coordinated attack on the tumor through independent orthogonal directions; a cellular therapeutic approach distinct from many others that rely on a single cell type or mechanism for the anti-tumor activity. SUPLEXA cells emerge following a simple co-incubation of ENLIST cells with patient-derived PBMC in the absence of any genetic engineering steps. We believe that, since SUPLEXA cells are activated through naturally-occurring receptors, they are likely to retain normal trafficking patterns and homeostatic mechanisms, suggesting a more efficacious and safe cellular therapy.
Alloplex’s proprietary ENgineered Leukocyte Immune STimulator cell line concept (ENLISTCELLS™) is protected by a combination of patent and trade secret.
In all preclinical experiments conducted to date, SUPLEXA cells demonstrated that they are broadly cytolytic against a variety of tumor cells but do not target normal naïve or activated immune cells, suggesting that the antitumor activity is both tumor-specific and HLA-independent.
The hypothesis that emerged during the pre-clinical phase was that SUPLEXA cells mount a coordinated attack on the tumor through independent orthogonal mechanisms consistent with the nature of the various immune cell types involved; hence a cellular therapeutic approach distinct from many others that rely on a single immune cell type or cancer antigen (e.g. CAR-T cell).
The absence of any genetic alterations in SUPLEXA therapy also brought profound functional benefits; such as retention of natural homeostatic mechanisms as well as commercial benefits that derive from a low cost of goods.
Preclinical data included successful SUPLEXA cell production even from heavily-compromised leukemic blood samples. Please review our ASCO oral presentation and poster.
Preclinical studies suggested that SUPLEXA therapeutic cells could represent a safe and effective therapy across tumor types. Feedback from a number of opinion-leaders at that time was, without exception, supportive of this view.
We have observed an excellent safety profile with no drug-related serious adverse events during the in-human clinical trials of SUPLEXA to date (July 2023). Any SAEs were classified as not related to SUPLEXA. The testing protocol, which was perfected over time, and incorporated increased dosing rates, has also unfolded without drug-related SAEs.
Signs of clinical activity in various tumor types are encouraging. These are consistent with broad pre-clinical in vitro activity. Exploratory CyTOF characterization, which has been conducted on all patients, demonstrates improved markers of immune health over initial time points.
Longitudinal blood samples from SUPLEXA-treated patients were immuno-profiled in order to identify SUPLEXA-induced changes over time. Analysis of the PBMC composition revealed rapid modulation of the myeloid components characterized by dramatic decreases in the number of myeloid derived suppressor cells combined with complementary increases in the number of activated monocytes. Based on what is known about these cell types, it appears these changes would strongly favor an enhanced anti-tumor immune response.
To render this idea commercially viable, we developed a reliable and robust manufacturing process which employs 50mls of patient whole blood, is manufactured under GMP conditions, resulting in multiple SUPLEXA therapeutic doses.
A first-in-human (phase 1) clinical trial to assess the safety and tolerability of this novel therapeutic and to provide early evidence of clinical anti-tumor activity is underway.
Alloplex appointed experienced clinical trial partners for this first-in-human clinical trial in Australia. The initial trial site was confirmed and the trial commenced in 2Q, 2022. The third, and final, trial site was confirmed in December 2022.
Trial participant requirements:
While Alloplex has opted for a variety of theoretical and strategic reasons to make its first-generation product autologous, there is a clear path to making a version of these therapeutic cells suitable for allogeneic administration as an off-the-shelf therapy and even integrating an engineering step, should one prove to be particularly advantageous.
Furthermore, there is significant potential to use SUPLEXA therapeutic cells:
National expenditures for cancer care worldwide continue to increase. Spending on cancer care in the US surpassed $200 billion1 in 2020.
Cancers are a leading cause of death worldwide, accounting for nearly 10 million deaths, or 1 in 6 deaths, in 20202. Furthermore, the number of new cancer cases per year is expected to rise to 29.5 million and the number of cancer-related deaths to 16.4 million by 20403.
Much of the cellular therapy landscape is focused on CAR-T, NK and CAR-NK, autologous dendritic cells and allogeneic dendritic cell lines, γδ-T cells, macrophages, B cells and TILs (tumor infiltrating lymphocytes).
While some alternative Phase 2-ready cellular approaches have significant patient burdens of surgical procedures, apheresis blood collections, and chemotherapy ablation, SUPLEXA requires less than 50mL of whole blood to manufacture a sufficient number of SUPLEXA therapeutic cells for an entire course of therapy.
1 Mariotto AB, Enewold L, Zhao J, Zeruto CA, Yabroff KR. Medical care costs associated with cancer survivorship in the United States.Cancer Epidemiol Biomarkers Prev. 2020;29(7):1304-1312. doi:10.1158/1055-9965.EPI-19-1534 PubMedGoogle ScholarCrossref Dieleman JL, Cao J, Chapin A, et al. US health care spending by payer and health condition, 1996-2016. JAMA. 2020;323(9):863-884. doi:10.1001/jama.2020.0734
2 WHO Cancer Factsheet.
3 The WHO’s International Agency For Research On Cancer.
SUPLEXA therapeutic cells is a unique non-engineered cellular therapy that demonstrates high potential to address a significant unmet medical need in a simple, reproducible and robust manner.
