Executive summary

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 an 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 Dr. 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 are projected to begin 4Q 2021.

  • “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.”

    Dr. Frank Borriello, MD, PhD

    Photo of Dr. Frank Borriello MD, PhD

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General company information

Alloplex is a privately-held company with operations in Boston, USA and a subsidiary in Melbourne, Australia.

Science and IP Milestones

Corporate and Finance Milestones

Science and IP Milestones
  • July - Dr. Frank Borriello, MD, PhD develops concept.
  • ENLISTCELLS trademark registered.
  • SUPLEXACELLS trademark registered.
Corporate and Finance Milestones
  • Alloplex Biotherapeutics Inc. registered.
2016
Science and IP Milestones
  • Initial experiments
  • Nov - US patent application (15/821,105) filed.
  • Nov - Patent applications filed in Australia, Japan and Korea.
Corporate and Finance Milestones
  • Jan - Dr. James A. Lederer, PhD appointed Chief Scientific Officer.
2017
Corporate and Finance Milestones
  • Scientific Advisory Board established.
  • Aug - Dr. Sharron Gargosky, PhD appointed Chief Development Officer.
2018
Science and IP Milestones
  • Oct - US Application 16/660,442 filed.
  • Nov - First poster presented at SITC.
Corporate and Finance Milestones
  • May - Alloplex Australia Pty Ltd registered.
  • Nov - Dr. Martin A. (Mac) Cheever, PhD appointment to Scientific Advisory Board.
2019
Science and IP Milestones
  • May - US patent application filed: "directed to mesenchymal stem cell lines and uses thereof".
  • Mid - First Xenograft study completed.
  • Aug - US Patent 10,731,128 issued.
Corporate and Finance Milestones
  • May - Dr. Robin Robinson, PhD appointed to Scientific Advisory Board.
2020
Science and IP Milestones
  • Mar - Second Xenograft study completed.
  • Aug - Third Xenograft study plus cytokines completion (est.).
  • Aug - Fourth Xenograft study completion (est.).
  • Robust data of successful SUPLEXA cell production.
  • Robust data from heavily compromised leukaemia blood sample.
  • Q4 - SUPLEXA cells are Phase 1 development ready.
  • 2nd Half - First in-human clinical trial (target for commencement).
Corporate and Finance Milestones
  • Apr - Series A funding round (US$15m) for 1st in-human clinical trial (of SUPLEXA therapeutic cells) commences.
2021

Science and IP Milestones

Corporate and Finance Milestones

The team

Alloplex was founded by Dr. Frank Borriello MD, PhD, 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:

  • Dr. James Lederer, PhD, serving as CSO. Dr. Lederer who also holds an Associate Professorship of Surgery at the Brigham and Women’s Hospital and Harvard Medical School. He is an expert in the injury induced modulation of the immune system; and
  • Dr. Sharron Gargosky, PhD, as Chief Development Officer who has over 25 years of experience in global clinical development and operations, medical affairs, regulatory and manufacturing in the field of pharmaceutical and biologic development having managed international programs from early research phase through the U.S. Food & Drug Administration approval process.

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.

Concept and IP

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.

Alloplex Mark Logo

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 cell 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.

Patent Summary

Alloplex’s proprietary ENgineered Leukocyte Immune STimulator cell line concept (ENLISTCELLS™) is protected by a combination of patent and trade secret.

1 - Directed to Allogeneic Tumor Vaccines (Group A).

2 - Directed to Allogeneic Tumor Vaccines (Group B).

3 - Directed to Compositions and Methods for In Vitro Activation and Expansion of Serial Killer T Cell Populations and Passive Immunization of a Cancer Patient with Tumor Cell Killing Cells

The process

Hover graphic to expand points or click to view in a PDF.

SUPLEXA therapeutic cells are not engineered; they are reprogrammed to recognize and kill tumor cells.

  • Simple, inexpensive and reproducible manufacturing to date in the lab.
  • Successful technical transfer and GMP manufacturing.
  • No generic engineering.
  • No feeder cells required.
  • All GMP compatible non-xeno sourced reagents.
  • Routinely high yields with cell viabilities typically ~90%.
  • Requires only standard and readily available laboratory equipment.

Robust preclinical data

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 deriving from a low cost of goods.

Preclinical data includes successful SUPLEXA cell production from even heavily-compromised leukemic blood samples.

Safety & efficacy

SUPLEXA therapeutic cells exhibit:

  • Broad anti-tumor activity against tumor cell lines of diverse origin: suggestive of efficacy against cancer .
  • No cytolytic activity observed against normal autologous or allogeneic PBMC: suggestive of safety against normal resting cells.
  • No fratricide: SUPLEXA cells do not attack each other: suggestive of safety against normal activated cells.
  • As an autologous therapy:
    • No graft vs host activity disease to negatively impact the safety profile.
    • No host vs. graft activity to negatively impact the efficacy profile.
  • No potential for tumorigenic mutations mediated by DNA engineering techniques.
  • Low variability in cellular composition among normal healthy PBMC samples.

Preclinical studies to date 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.

Manufacturing process

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, hence eliminating 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.

  • Fast and simple

    Manufacturing of SUPLEXA therapeutic cells using ENLIST training cells is a simple defined process requiring no additional genetic engineering steps and no requirement for feeder cells. In just three weeks, the manufacturing process reliably yields a full course of treatment comprised of 4-6 weekly doses.

  • Robust

    All reagents are GMP-compatible and the resulting product displays a low inter-patient variability with routinely high cell yields.

  • Relatively inexpensive

    With the requirement for only standard laboratory equipment, manufacturing of SUPLEXA therapeutic cells requires a significantly lower cost of goods compared with genetically engineered forms of cellular therapy.

Clinical

Phase 1 clinical trial

Plans are underway to start a first-in-human, phase 1 clinical trial to assess the safety and tolerability of this novel therapeutic but also 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. Trial sites are confirmed, and the trial is targeted to commence in 4Q 2021.

Trial participant requirements:

  • Cancer patients with measurable disease, irrespective of tumor type, provided that the patient is not concomitantly receiving or under the influence of an immunosuppressive therapy.
  • The open label trial designed is expected to yield an accruing body of data on both safety and efficacy over a 12-18 month period.

Vision beyond first-generation product

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.

Market considerations

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 only a few tubes of whole blood to manufacture a sufficient number of SUPLEXA therapeutic cells for an entire course of therapy in just several weeks.


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 are 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.

R&D competitive space

The Cellular Therapy competitive landscape

SUPLEXA therapeutic cell differentiation.

FEATURE

SUPLEXA
Cells

Tumor Infiltrating Lymphocytes (1st gen)

CAR-T cells
(1st gen)

 

CAR-T cells
(2nd gen)

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
or off-the-shelf

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/
cost

Simple / inexpensive

Complex / expensive

Complex / expensive

Complex / expensive

Complex / expensive

Simple / inexpensive

Complex / expensive

Simple / inexpensive

Complex/
Expensive

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