Enumeral

Last updated
Enumeral Biomedical Holdings, Inc.
Type Public
OTCQB:  ENUM
Industry Biotechnology
FoundedDecember 11, 2009 (2009-12-11)
DefunctJanuary 29, 2018 (2018-01-29)
FateAssets sold to Xoma Corporation during bankruptcy
Headquarters
Cambridge, Massachusetts [1]
,
United States
Key people
  • John Rydzewski (Chairman)
  • Kevin G. Sarney (interim CEO, 2018) [2] : Signatures 
Products Monoclonal antibodies targeting immune checkpoint proteins
Number of employees
10 (2017) [3]
Website www.enumeral.com

Enumeral was a Cambridge, Massachusetts-based biotechnology company which developed monoclonal antibody immunotherapies through an 'immunoprofiling' platform that allowed it to scan the human immune microenvironment and identify and validate potential drug candidates. The company filed for Chapter 11 bankruptcy and arranged to sell its assets to Xoma Corporation in January 2018.

Contents

The company

Enumeral was founded in 2009 to bring together various immunoprofiling technologies from Harvard University, Massachusetts Institute of Technology, the Whitehead Institute for Biomedical Research and Massachusetts General Hospital. [4] The company's Scientific Founder was Christopher Love, Associate Professor of Chemical Engineering at MIT; [5] the Executive Chairman is John Rydzewskand and its CEO is Arthur Tinkelenberg. In 2014 the company was taken public through a reverse takeover into a shell called Cerulean Group. Its stock is traded OTC in the US, with trading in the OTCQB marketplace tier commencing on 4 August 2014. [6] The stock code is ENUM.

By 2015, Enumeral had completed pre-clinical development of PD-1 inhibitors and sought partners to enter clinical development with. [3] In December 2016, Enumeral completed raising US$3.4 million to fund long-term development plans, but by May 2017, the company announced it only had sufficient cash on hand to fund operations through June 2017. [3] [7] [8] Shortly thereafter, in June, the company dismissed its R&D research staff. [9] In August 2017, Enumeral was kicked out of its headquarters in Cambridge due to non-payment of rent and other fees. [10] The Cambridge headquarters was also the home of Celgene and Unum Therapeutics. [7] By the time the company lost its headquarters, Arthur Tinkelenberg was being described as the company's "former president and chief executive officer". [10] In January 2018, Enumeral struck a deal with Xoma Corporation, located in the San Francisco Bay Area, to sell its assets for US$1.6 million, while concurrently filing for Chapter 11 bankruptcy. [1] [2] : item 1.03 

Platform

Enumeral's platform consists of various proprietary cellular libraries derived from target-specific immunized sources or from human patient donors. The platform has three main parts:

Anti PD-1 antibodies

An early commercial interest of Enumeral has focused on PD-1, currently targeted by two FDA-approved monoclonal antibody drugs - Keytruda, from Merck & Co., and Opdivo, from Bristol-Myers Squibb. In 2015 Enumeral reported that it had used its platform to raise anti-PD-1 antibodies that did not compete with Keytruda or Opdivo for binding to PD-1, nor did they appear to compete with PD-1's ligand, PD-L1. These potentially allosteric antibodies also produced more interferon gamma and showed dose-dependent increases in T cell CD25 expression. [21] Further, Enumeral's antibodies caused higher T cell activation in ex vivo human assays than the currently marketed anti-PD-1 antibodies [22] and, in that same setting, in combination with one of the marketed antibodies, could elicit an additive effect on T cell activation. [23] Enumeral expects to take an anti-PD-1 antibody into clinical testing in 2016. [24]

Merck collaboration

In December 2014 Enumeral announced a collaboration with Merck & Co. in which the two companies would use the Enumeral platform to interrogate the tumor microenvironment in colorectal cancer tissues obtained directly from patients, with the aim of identifying functional cellular responses to Merck-developed immuno-oncology products. [25] In September 2015 Enumeral announced that the Merck collaboration had achieved its first milestone, enabling Enumeral to receive a milestone payment from Merck. [26]

Related Research Articles

<span class="mw-page-title-main">Cytokine</span> Broad and loose category of small proteins important in cell signaling

Cytokines are a broad and loose category of small proteins important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.

<span class="mw-page-title-main">Natural killer cell</span> Type of cytotoxic lymphocyte

Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Most immune cells detect the antigen presented on major histocompatibility complex (MHC) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

<span class="mw-page-title-main">Interleukin 10</span> Anti-inflammatory cytokine

Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, interleukin 10 is encoded by the IL10 gene. IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term stromal comes from Latin stromat-, "bed covering", and Ancient Greek στρῶμα, strôma, "bed".

Agenus Inc. is a Lexington, Massachusetts-based biotechnology company focused on immunotherapy including immuno-oncology, a field that uses the immune system to control or cure cancer. The company is developing checkpoint modulators (CPMs), patient-specific anti-cancer vaccines, and adjuvants desugned for use with various vaccines. CPM development is a particularly fast-moving field, since early products have produced unprecedented clinical benefits for patients.

<span class="mw-page-title-main">Monoclonal antibody therapy</span> Form of immunotherapy

Monoclonal antibodies (mAbs) have varied therapeutic uses. It is possible to create a mAb that binds specifically to almost any extracellular target, such as cell surface proteins and cytokines. They can be used to render their target ineffective, to induce a specific cell signal, to cause the immune system to attack specific cells, or to bring a drug to a specific cell type.

<span class="mw-page-title-main">CXCL9</span> Mammalian protein found in Homo sapiens

Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.

CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, macrophages, and certain T cells. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.

<span class="mw-page-title-main">CD137</span> Member of the tumor necrosis factor (TNF) receptor family

CD137, a member of the tumor necrosis factor (TNF) receptor family, is a type 1 transmembrane protein, expressed on surfaces of leukocytes and non-immune cells. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB, and induced by lymphocyte activation (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule, and as a potential target in cancer immunotherapy.

Antigenic escape, immune escape, immune evasion or escape mutation occurs when the immune system of a host, especially of a human being, is unable to respond to an infectious agent: the host's immune system is no longer able to recognize and eliminate a pathogen, such as a virus. This process can occur in a number of different ways of both a genetic and an environmental nature. Such mechanisms include homologous recombination, and manipulation and resistance of the host's immune responses.

<span class="mw-page-title-main">Cancer immunology</span> Study of the role of the immune system in cancer

Cancer immunology (immuno-oncology) is an interdisciplinary branch of biology and a sub-discipline of immunology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.

<span class="mw-page-title-main">Programmed cell death protein 1</span> Mammalian protein found in Homo sapiens

Programmed cell death protein 1(PD-1),. PD-1 is a protein encoded in humans by the PDCD1 gene. PD-1 is a cell surface receptor on T cells and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.

<span class="mw-page-title-main">Interleukin-17A</span> Protein-coding gene in the species Homo sapiens

Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.

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<span class="mw-page-title-main">Immune checkpoint</span> Regulators of the immune system

Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets.

<span class="mw-page-title-main">PD-1 and PD-L1 inhibitors</span> Class of anticancer drugs

PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PDL1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer.

Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect themselves from attack by stimulating immune checkpoint targets. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. The first anti-cancer drug targeting an immune checkpoint was ipilimumab, a CTLA4 blocker approved in the United States in 2011.

<span class="mw-page-title-main">CD28 family receptor</span> Group of regulatory cell surface receptors

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References

  1. 1 2 Keown, Alex (February 7, 2018). "Cambridge's Enumeral Filed for Bankruptcy, Sells Assets to Bay Area's XOMA". BioSpace. Retrieved July 21, 2018.
  2. 1 2 Form 8-K: Enumeral Biomedical Holdings, Inc (Report). U.S. Securities and Exchange Commission. January 26, 2018. Retrieved July 20, 2018.
  3. 1 2 3 Keown, Alex (May 30, 2017). "Cambridge Biotech Enumeral Biomedical Has Cash to Fund Its Operations Only Into Next Month". BioSpace. Retrieved July 20, 2018.
  4. ↑ "10-Q: Enumeral Biomedical Holdings Inc". Marketwatch.com. Retrieved 28 December 2015.
  5. ↑ "Enumeral Biomedical Raises $21.5 Million from New and Current Investors, Begins Public Trading". www.sec.gov. 4 August 2014. Retrieved 2023-12-07.
  6. ↑ "Enumeral Biomedical Raises $21.5 Million from New and Current Investors, Begins Public Trading" (Press release). Enumeral. August 4, 2014. Archived from the original on March 22, 2015. Retrieved December 27, 2015.
  7. 1 2 Stendahl, Max (May 26, 2017). "Cambridge biotech Enumeral faces uncertain future as cash dries up". Boston Business Journal. Retrieved July 20, 2018.
  8. ↑ "Enumeral Biomedical believes it has sufficient cash to continue to explore strategic alternatives only into July 2017". Reuters. 26 June 2017. Retrieved 7 December 2023.
  9. ↑ Terry, Mark (June 20, 2017). "Faltering Enumeral Biomedical Cuts R&D Staff, Alters Executive Compensation Deal". BioSpace. Retrieved July 20, 2018.
  10. 1 2 Terry, Mark (August 29, 2017). "Enumeral Biomedical Gets Evicted as it Winds Down Operations". BioSpace. Retrieved July 20, 2018.
  11. ↑ Love JC; Ronan JL; Grotenbreg GM; van der Veen AG; Ploegh HL (June 1, 2006). "A microengraving method for rapid selection of single cells producing antigen-specific antibodies". Nat. Biotechnol. 24 (6): 703–7. doi:10.1038/nbt1210. PMID   16699501. S2CID   2369641. Closed Access logo transparent.svg
  12. ↑ Bradshaw EM; Kent SC; Tripuraneni V; Orban T; Ploegh HL; Hafler DA; Love JC (October 1, 2008). "Concurrent detection of secreted products from human lymphocytes by microengraving: cytokines and antigen-reactive antibodies". Clin Immunol. 129 (1): 10–18. doi:10.1016/j.clim.2008.06.009. PMC   2577144 . PMID   18675591.
  13. ↑ Story CM; Papa E; Hu CC; Ronan JL; Herlihy K; Ploegh HL; Love JC. (November 18, 2008). "Profiling antibody responses by multiparametric analysis of primary B cells". Proc Natl Acad Sci U S A. 105 (46): 17902–7. Bibcode:2008PNAS..10517902S. doi: 10.1073/pnas.0805470105 . PMC   2584674 . PMID   19004776.
  14. ↑ Han Q; Bradshaw EM; Nilsson B; Hafler DA; Love JC (June 7, 2010). "Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving". Lab Chip. 10 (11): 1391–1400. doi:10.1039/b926849a. PMC   3128808 . PMID   20376398.
  15. ↑ Varadarajan N; Julg B; Yamanaka YJ; Chen H; Ogunniyi AO; McAndrew E; Porter LC; Piechocka-Trocha A; Hill BJ; Douek DC; Pereyra F; Walker BD; Love JC (November 1, 2011). "A high-throughput single-cell analysis of human CD8⁺ T cell functions reveals discordance for cytokine secretion and cytolysis". J Clin Invest. 121 (11): 4322–31. doi:10.1172/JCI58653. PMC   3204845 . PMID   21965332.
  16. ↑ Adalsteinsson VA; Tahirova N; Tallapragada N; Yao X; Campion L; Angelini A; Douce TB; Huang C; Bowman B; Williamson CA; Kwon DS; Wittrup KD; Love JC (October 5, 2013). "Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines". Integrative Biology. 5 (10): 1272–81. doi:10.1039/c3ib40059j. PMC   4034677 . PMID   23995780.
  17. ↑ Chattopadhyay PK; Gierahn TM; Roederer M; Love JC (February 1, 2014). "Single-cell technologies for monitoring immune systems". Nat Immunol. 15 (2): 128–35. doi:10.1038/ni.2796. PMC   4040085 . PMID   24448570.
  18. ↑ Zhou P; Shaffer DR; Alvarez Arias DA; Nakazaki Y; Pos W; Torres AJ; Cremasco V; Dougan SK; Cowley GS; Elpek K; Brogdon J; Lamb J; Turley SJ; Ploegh HL; Root DE; Love JC; Dranoff G; Hacohen N; Cantor H; Wucherpfennig KW (February 6, 2014). "In vivo discovery of immunotherapy targets in the tumour microenvironment". Nature. 506 (7486): 52–7. Bibcode:2014Natur.506...52Z. doi:10.1038/nature12988. PMC   4052214 . PMID   24476824.
  19. ↑ "Enumeral Scientific Advisory Board". Enumeral.com. Archived from the original on January 5, 2016. Retrieved 28 December 2015.[ self-published source ]
  20. ↑ Lohr JG; Adalsteinsson VA; Cibulskis K; Choudhury AD; Rosenberg M; Cruz-Gordillo P; Francis JM; Zhang CZ; Shalek AK; Satija R; Trombetta JJ; Lu D; Tallapragada N; Tahirova N; Kim S; Blumenstiel B; Sougnez C; Lowe A; Wong B; Auclair D; Van Allen EM; Nakabayashi M; Lis RT; Lee GS; Li T; Chabot MS; Ly A; Taplin ME; Clancy TE; Loda M; Regev A; Meyerson M; Hahn WC; Kantoff PW; Golub TR; Getz G; Boehm JS; Love JC. (May 1, 2014). "Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer" (PDF). Nat. Biotechnol. 32 (5): 479–84. doi:10.1038/nbt.2892. PMC   4034575 . PMID   24752078.
  21. ↑ "Enumeral Announces Identification of Anti-PD-1 Antibodies with Potential for Differentiated Mechanism of Action" (Press release). Enumeral. September 24, 2015. Archived from the original on January 5, 2016. Retrieved December 28, 2015.[ self-published source ]
  22. ↑ "Enumeral Reports That Its Novel Class of Anti-PD-1 Antibodies Elicits Higher T Cell Activation in Ex Vivo Human Assays than Currently Marketed Anti-PD-1 Antibodies" (Press release). Enumeral. November 3, 2015. Archived from the original on January 5, 2016. Retrieved 28 December 2015.[ self-published source ]
  23. ↑ "Enumeral Reports That Its Novel Class of Potentially Allosteric Anti-PD-1 Antibodies Can Elicit an Additive Effect on T Cell Activation in Ex Vivo Human Assays When Used in Combination With A Currently Marketed Anti-PD-1 Antibody" (Press release). Enumeral. November 18, 2015. Archived from the original on January 5, 2016. Retrieved 27 December 2015.[ self-published source ]
  24. ↑ "Enumeral Expands Scientific Advisory Board to Support Development of Novel Immunomodulators" (Press release). Enumeral.com. June 4, 2015. Archived from the original on January 5, 2016. Retrieved 28 December 2015.[ self-published source ]
  25. ↑ "Enumeral and Merck Form Collaboration for Predicting Clinical Drug Response with Human-driven Immune Profiling Platform" (Press release). Enumeral.com. December 18, 2014. Archived from the original on January 5, 2016. Retrieved 27 December 2015.[ self-published source ]
  26. ↑ "Enumeral Achieves First Milestone in Merck Collaboration" (Press release). Enumeral.com. September 8, 2015. Archived from the original on January 5, 2016. Retrieved 28 December 2015.[ self-published source ]
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