Alloplex has developed a highly differentiated, non-engineered cellular therapy with exceptional promise to treat a broad range of cancers in a cost-effective manner.
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 (2021) comprised exclusively of several approved CAR-T products. Researchers are expanding on this early success by adding additional features to CAR-T cells drug candidates as well as exploring other cell types to engineer such as NK, γδ-T 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 cellular manufacturing reagents, 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 patent for proprietary ENLIST cells.
Nonclinical research suggests SUPLEXA therapeutic cells will be well-tolerated and safe. GMP manufacturing is well-established and first-in-human phase 1 clinical trials commenced in 2Q, 2022.
“The SUPLEXA approach has proven remarkably robust and, without exception, highly efficacious in all preclinical experiments conducted to date across a broad range of tumor cell types.”
In the large, dynamic and highly competitive field of cellular therapies, the ultimate goal is to deliver not only an efficacious and safe product that is well-tolerated but one which is also affordable and accessible.
Alloplex presents a rare 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.
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 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:
Since 2019, 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. In contrast, the individual activation of these same pathways led to little 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 therapy 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 have demonstrated that they are broadly cytolytic against a variety 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 emerging hypothesis is 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 brings 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 includes successful SUPLEXA cell production from even heavily-compromised leukemic blood samples.
SUPLEXA therapeutic cells exhibit:
To date, preclinical studies suggest that SUPLEXA therapeutic cells could represent a safe and effective therapy across tumor types. Feedback from a number of opinion-leaders have been, without exception, supportive of this view.
To render this idea commercially viable, we have developed a manufacturing process capable of yielding multiple SUPLEXA therapeutic cell doses in a fast, simple, robust and cost-effective manner. This eliminates most of the liabilities historically attributed to autologous therapies and thereby improving the accessibility and affordability of this new class of cellular therapy.
The manufacturing of ENLIST cells, a key component, is fast, simple, robust and relatively inexpensive.
Plans are underway to start 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.
Alloplex has appointed an experienced clinical trial partner for the first-in-human clinical trial in Australia. Initial clinical trial sites are confirmed and the trial commenced in 2Q, 2022.
Trial participant requirements:
While Alloplex has opted to make its first-generation product autologous for a variety of theoretical and strategic reasons, 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.
National expenditures for cancer care worldwide continue to increase. According to the National Cancer Institute Cancer Trends Progress Report, estimated national expenditures for cancer care in the United States reached US$150.8 billion1 in 2018.
In 2020, cancers are a leading cause of death worldwide, accounting for nearly 10 million deaths, or 1 in 6 deaths2. 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 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 just several weeks, and only a few tubes of whole blood to manufacture a sufficient number of SUPLEXA therapeutic cells for an entire course of therapy.
1-Data up to date as of March 2020.
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 fast, simple, robust and cost-effective manner.
SUPLEXA therapeutic cell differentiation.
|
FEATURE |
SUPLEXA |
Tumor Infiltrating Lymphocytes (1st gen) |
CAR-T cells
|
CAR-T cells |
CAR-macrophages |
NK |
CAR-NK |
γδ-T cells |
CAR-γδ-T cells |
|
Stage of development |
Phase 1 ready |
Late-stage clinical |
Commercial |
Early-stage clinical |
Pre-clinical |
Late-stage clinical |
Late-stage clinical |
Early-stage clinical |
Early-stage clinical |
|
Source |
Individualized (autologous) |
Individualized |
Individualized |
Off-the-shelf (allogeneic) |
Individualized |
Individualized or off-the-shelf |
Individualized |
Individualized or off-the-shelf |
Individualized or off-the-shelf |
|
Starting material |
Whole blood |
Patient tumor |
Leukopheresis procedure |
Leukopheresis procedure |
Leukopheresis procedure |
Whole blood |
Leukopheresis procedure |
Whole blood |
Leukopheresis procedure |
|
Spectrum of anti-tumor activity |
Broad |
N/A |
Narrow |
Narrow |
Narrow |
Broad |
Narrow |
Broad |
Narrow |
|
Cell type(s) |
Multiple NK cell, NKT cell, γδ-T cell, CD8+ T cell and CD4+ cell |
Single CD8+ T cells (mostly) |
Single CD8+ T cells (mostly) |
Single CD8+ T cells (mostly) |
Single Macrophages |
Single NK cell |
Single NK cell |
Single γδ-T cells |
Single γδ-T cells
|
|
Engineering required |
No |
No |
Yes |
Yes |
Yes |
No |
Yes |
No |
Yes |
|
Manufacturing/ |
Simple / inexpensive |
Complex / expensive |
Complex / expensive |
Complex / expensive |
Complex / expensive |
Simple / inexpensive |
Complex / expensive |
Simple / inexpensive |
Complex/ |
|
No. of doses |
Multiple |
TBD |
Single |
TBD |
TBD |
TBD |
TBD |
TBD |
TBD |
|
Preconditioning |
TBD |
TBD |
Yes |
TBD |
TBD |
TBD |
TBD |
TBD |
TBD |
Chimeric Antigen Receptors (CAR) – receptors designed to recognize a specific tumor antigen