Enumeral

For categorical values in programming languages, see enumerated type.
Enumeral
Public
Traded as OTCQB: ENUM
Industry Biotechnology
Founded 2009
Headquarters Cambridge, Ma.
Key people
 John Rydzewski
(Chairman)
Arthur Tinkelenberg
(CEO)
Products Monoclonal antibodies targeting immune checkpoint proteins
Website www.enumeral.com

Enumeral is a US biotechnology company which develops monoclonal antibody immunotherapies through an 'immunoprofiling' platform that allows it to scan the human immune microenvironment and identify and validate potential drug candidates. The company’s initial focus is on immunomodulators that target immune checkpoint proteins. The initial checkpoints targeted are PD-1, TIM3, LAG3, TIGIT, VISTA and OX40.

The company

Enumeral was founded in 2009[1] to bring together various immunoprofiling technologies from Harvard University, Massachusetts Institute of Technology, the Whitehead Institute for Biomedical Research and Massachusetts General Hospital. The company's Scientific Founder is Christopher Love, Associate Professor of Chemical Engineering at MIT; the Executive Chairman is John Rydzewskand its s 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.[2] The stock code is ENUM.

The firm is headquartered in Cambridge, Ma..

Platform

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

* Microengraving. This platform has its origins in work which Love et al. published in the journal Nature Biotechnology in 2006. Their foundational paper showed that it was possible to quickly capture a large mass of antibody-producing cells through engraved microarrays based on intaglio printing, where those arrays were carrying the secreted products of single cells.[3] The Love group elaborated on the utility of this microengraving technology in 2008 in two key papers. In the first they applied it to PBMCs from a Type I diabetic patient and reported that a small percentage of CD19+ B cells were secreting proinsulin-reactive antibodies.[4] In the second they showed how the technology could be used to describe the different kinds of antibodies produced during a multipart vaccination.[5] In 2010 the Love lab demonstrated that its microengraving technology could be used to quantify the rates of secretion of up to four cytokines simultaneously released from individual viable primary immune cells, and that, among other things, primary T cells with specific profiles of secretion could be recovered and expanded in vitro.[6] In 2011 the Love lab provided proof that microengraving would allow multiple fresh CD8+ T cells to be evaluated for their cytotoxic activity and cytokine secretion.[7] A 2013 paper from the Love lab reported the use of microengraving in evaluating the expression of pro-angiogenic ELR+ CXC chemokines by colorectal tumor and stromal cells.[8] The Love lab published a review on various single-cell technologies for monitoring immune systems, including the microengraving approach, in Nature Immunology in 2014.[9]

* Checkpoint discovery. This technology allows new immune checkpoints in T cells to be discovered. It does so through the identification of small hairpin RNA molecules involved in the release of blocks on T-cell proliferation at the time of tumour antigen recognition. This technology was discovered in the laboratory of Dr Kai Wucherpfennig at the Dana–Farber Cancer Institute and was published in Nature in 2014.[10] Kai Wucherpfennig currently serves on Enumeral's Scientific Advisory Board.[11]

* Whole-exome sequencing. This technology, first unveiled in Nature Biotechnology in 2014, involves the sequencing of whole exomes of circulating tumor cells by means of cell enrichment and isolation, genomic amplification, library qualification and 'census-based' sequencing.[12]

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.[13] Further, Enumeral's antibodies caused higher T cell activation in ex vivo human assays than the currently marketed anti-PD-1 antibodies[14] and, in that same setting, in combination with one of the marketed antibodies, could elicit an additive effect on T cell activation.[15] Enumeral expects to take an anti-PD-1 antibody into clinical testing in 2016.[16]

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.[17] In September 2015 Enumeral announced that the Merck collaboration had achieved its first milestone, enabling Enumeral to receive a milestone payment from Merck.[18]

References

  1. ↑ "10-Q: Enumeral Biomedical Holdings Inc". Marketwatch.com. Retrieved 28 December 2015.
  2. ↑ "Enumeral Biomedical Raises $21.5 Million from New and Current Investors, Begins Public Trading". Enumeral.com. August 4, 2014. Retrieved 27 December 2015.
  3. ↑ 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.
  4. ↑ 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 2577144Freely accessible. PMID 18675591.
  5. ↑ 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. doi:10.1073/pnas.0805470105. PMC 2584674Freely accessible. PMID 19004776.
  6. ↑ 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 3128808Freely accessible. PMID 20376398.
  7. ↑ 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 3204845Freely accessible. PMID 21965332.
  8. ↑ 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.". Integr Biol (Camb). 5 (10): 1272–81. doi:10.1039/c3ib40059j. PMC 4034677Freely accessible. PMID 23995780.
  9. ↑ 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 4040085Freely accessible. PMID 24448570.
  10. ↑ 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. doi:10.1038/nature12988. PMC 4052214Freely accessible. PMID 24476824.
  11. ↑ "Enumeral Scientific Advisory Board". Enumeral.com. Retrieved 28 December 2015.
  12. ↑ 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.". Nat. Biotechnol. 32 (5): 479–84. doi:10.1038/nbt.2892. PMC 4034575Freely accessible. PMID 24752078.
  13. ↑ "Enumeral Announces Identification of Anti-PD-1 Antibodies with Potential for Differentiated Mechanism of Action". Enumeral.com. September 24, 2015. Retrieved December 28, 2015.
  14. ↑ "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". Enumeral.com. November 3, 2015. Retrieved 28 December 2015.
  15. ↑ "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". Enumeral.com. November 18, 2015. Retrieved 27 December 2015.
  16. ↑ "Enumeral Expands Scientific Advisory Board to Support Development of Novel Immunomodulators". Enumeral.com. June 4, 2015. Retrieved 28 December 2015.
  17. ↑ "Enumeral and Merck Form Collaboration for Predicting Clinical Drug Response with Human-driven Immune Profiling Platform". Enumeral.com. December 18, 2014. Retrieved 27 December 2015.
  18. ↑ "Enumeral Achieves First Milestone in Merck Collaboration". Enumeral.com. September 8, 2015. Retrieved 28 December 2015.
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