Filed Pursuant to Rule 424(b)(3) and Rule 424(c)
Registration No. 333-198847
Prospectus Supplement No. 16
(To Prospectus filed on July 6, 2015, as supplemented
by Prospectus Supplement No. 1 dated July 14, 2015, Prospectus Supplement No. 2 dated July 28, 2015, Prospectus Supplement No. 3 dated August 4, 2015, Prospectus Supplement No. 4 dated August 12, 2015, Prospectus Supplement No. 5 dated September 17, 2015, Prospectus Supplement No. 6 dated September 18, 2015, Prospectus Supplement No. 7 dated September 24, 2015, Prospectus Supplement No. 8 dated September 25, 2015, Prospectus Supplement No. 9 dated September 30, 2015, Prospectus Supplement No. 10 dated October 2, 2015, Prospectus Supplement No. 11 dated November 3, 2015, Prospectus Supplement No. 12 dated November 10, 2015, Prospectus Supplement No. 13 dated November 18, 2015, Prospectus Supplement No. 14 dated December 1, 2015, and Prospectus Supplement No. 15 dated December 8, 2015)
ENUMERAL BIOMEDICAL HOLDINGS, INC.
This Prospectus Supplement No. 16 supplements the information contained in the Prospectus, dated as of July 6, 2015, as amended by Prospectus Supplement No. 1 dated July 14, 2015, Prospectus Supplement No. 2 dated July 28, 2015, Prospectus Supplement No. 3 dated August 4, 2015, Prospectus Supplement No. 4 dated August 12, 2015, Prospectus Supplement No. 5 dated September 17, 2015, Prospectus Supplement No. 6 dated September 18, 2015, Prospectus Supplement No. 7 dated September 24, 2015, Prospectus Supplement No. 8 dated September 25, 2015, Prospectus Supplement No. 9 dated September 30, 2015, Prospectus Supplement No. 10 dated October 2, 2015, Prospectus Supplement No. 11 dated November 3, 2015, Prospectus Supplement No. 12 dated November 10, 2015, Prospectus Supplement No. 13 dated November 18, 2015, Prospectus Supplement No. 14 dated December 1, 2015, and Prospectus Supplement No. 15 dated December 8, 2015, relating to the resale of up to 52,154,760 shares of our common stock by selling stockholders.
This Prospectus Supplement No. 16 is being filed to include the information set forth in our Current Report on Form 8-K, which was filed with the Securities and Exchange Commission on January 8, 2016.
You should read this Prospectus Supplement No. 16 in conjunction with the Prospectus. This Prospectus Supplement No. 16 is qualified by reference to the Prospectus, except to the extent that the information contained in this Prospectus Supplement No. 16 supersedes the information contained in the Prospectus. This Prospectus Supplement No. 16 is not complete without, and may not be utilized except in connection with, the Prospectus.
You should consider carefully the risks that we have described in “Risk Factors” beginning on page 7 of the Prospectus.
Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.
The date of this Prospectus Supplement is January 8, 2016
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):January 8, 2016
Enumeral Biomedical Holdings, Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 000-55415 | 99-0376434 |
| (State or Other Jurisdictionof Incorporation) | (Commission File Number) | (I.R.S. Employer Identification Number) |
200 CambridgePark Drive, Suite 2000 Cambridge, Massachusetts (Address of Principal Executive Offices) |
02140 (Zip Code) |
(617) 945-9146
(Registrant’s telephone number, including area code)
N/A
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Item 7.01 Regulation FD Disclosure.
Enumeral Biomedical Holdings, Inc. (the “Company”) may use two presentations, in whole or in part, from time to time in presentations to potential partners, investors, analysts and others. Copies of the presentations are furnished as Exhibit 99.1 to this Current Report on Form 8-K and incorporated by reference herein. Copies of these presentations are also available on the Company’s website at www.enumeral.com.
The information in this Item 7.01 of this Current Report on Form 8-K and in the accompanying Exhibit 99.1 shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained in this Item 7.01 of this Current Report on Form 8-K and in the accompanying Exhibit 99.1 shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit Number | Description
| |
| 99.1 | Enumeral Biomedical Holdings, Inc. January 2016 Presentation Entitled “Discovery and Functional Characterization of Novel Anti-PD-1 Antibodies Using Ex Vivo Cell-Based Assays, Single-Cell Immunoprofiling, and In Vivo Studies in Humanized Mice” | |
| 99.2 | Enumeral Biomedical Holdings, Inc. January 2016 Presentation Entitled “Determination of Expressed T Cell Receptor Sequences of Single Human T Cells Isolated After Functional Profiling” |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| ENUMERAL BIOMEDICAL HOLDINGS, INC. | |||
| Dated: January 8, 2016 | By: | /s/ Kevin G. Sarney | |
| Name: Kevin G. Sarney | |||
| Title: Vice President of Finance, Chief Accounting Officer and Treasurer | |||
EXHIBIT INDEX
| Exhibit No. | Description | |
| 99.1 | Enumeral Biomedical Holdings, Inc. January 2016 Presentation Entitled “Discovery and Functional Characterization of Novel Anti-PD-1 Antibodies Using Ex Vivo Cell-Based Assays, Single-Cell Immunoprofiling, and In Vivo Studies in Humanized Mice” | |
| 99.2 | Enumeral Biomedical Holdings, Inc. January 2016 Presentation Entitled “Determination of Expressed T Cell Receptor Sequences of Single Human T Cells Isolated After Functional Profiling” |
Exhibit 99.1
B Discovery and Functional Characterization of Novel Anti-PD-1 Antibodies Using Ex VivoCell-Based Assays, Single-Cell Immunoprofiling, and In Vivo Studies in Humanized Mice Abstract Given recent approvals of anti-PD-1 inhibitors Keytruda (pembrolizumab)andOpdivo(nivolumab)fortreatmentofmetastatic melanomaandnon-smallcelllungcancerNSCLC,weaskedwhether additionalanti-PD-1inhibitorswithdifferentepitopesorpotentially differentiated mechanisms of action can provide clinical benefit beyondthetwomarketedtherapies.UsingEnumeral’sproprietary single cell technology, we generated more than 300 anti-PD-1 monoclonalantibodiesfromprimaryBcells.Bioinformaticsanalysisof sequences show these antibodies comprise 26 distinct clades, or families, that bind to PD-1. Results from binding studies further indicatewehavediscoveredafamilyofnovelantibodiesthatdonot appeartocompetewithcurrentlymarketedantibodiesforbindingto PD-1, nor do they appear to compete with PD-L1, suggesting a differentiatedmechanismofaction.Wehavehumanizedtwolead antibodiesforpreclinicaltestingandinpreparationforclinicalstudies. Here we describe functional characterization of the two lead antibodies using cell-based ex vivo assays, patient-derived tumor profilingassaysusingoursingle-cellplatform,andinvivostudiesin humanized NSG mice. Results show that the two lead anti-PD-1 antibodies exhibit a higher level of T cell activation in mixed lymphocytereaction(MLR)assaysusingprimaryhumanimmunecells. Second, these antibodies also demonstrated dose-dependent increasesinTcellCD25expression.Next,totesttheeffectofthetwo leadanti-PD-1antibodiesontumorgrowth,weconductedastudy usingapatient-derivedtumor(PDX)modelonhumanizedNSGmice. NSG mice reconstitute a full human immune systemincluding a functionalT,Bcellrepertoire,enablingthedirect,invivoevaluationof ourhumananti-PD-1antibodies. Figure 1. (A) Enumeral TargetDiscovery and (B) AntibodyDiscoveryPlatformsOverview (A)Analysisoftumorinfiltratedlymphocytes(TILs)ICexpression atthesinglecellfromhumantumorbiopsyusingEnumeral’s proprietarytechnology.Eachsinglecellisprofiledforsurface markerexpression,cytokinesecretion,andsubmittedforNGS. (B)Aftertargetidentification,immunizedanimalsarescreened using Enumeralmicro-engravingtechnology. Afterretrievalof antibody-secretingcells,heavyandlightchainsarerecoveredby single cell RT-PCR. Then, antibodies are cloned, tested for binding,andcharacterizedbiochemicallyandfunctionally. Conclusion Enumeral developed novel, fully humanized PD-1 blocking monoclonal antibodies, 388D4 and 244C8. 244C8 family of antibodies appears to have a novel mechanism of action, as they neither compete with currently marketed PD-1 antibodies for binding to PD-1 nor with PD-L1 binding, but induce expression of the high affinity IL-2 receptor alpha chain CD25. Both 388D4 and 244C8 can reverse T cell suppression in ex vivo TIL experiments in a subset of patient samples at least as potently as nivolimumab. Importantly, both 388D4 and 244C8 exhibited significant anti-tumor efficacy when tested in a NSCLC lung PDX model in vivo. These results demonstrate both ex vivo and in vivo function by our novelanti-PD-1 antibodies. B Figure 2. In Vitro Blockade with Enumeral’s anti-PD-1 AntibodiesCanRestoreTcellImmunity Enumeralanti-PD-1leadcandidatesweretestedfordifferentialTcell activationinresponsetoPD-1blockade invitro.Top2leadswere humanizedandtestedinamixedlymphocytereactionafter6daysof co-incubation of HLA-mismatched T cells and monocyte derived dendritic cells. T cell activation was assessed as inferred by secretion of effector cytokines such as interferon gamma (IFN?)(A)andupregulationofthehighaffinityIL-2receptorCD25 (B). Figure4.StudyoutlineforNSGPDXstudy 75humanized-NSGmicewereimplantedwithalungtumorPDX derived from a patient with metastatic non
Exhibit 99.2
1sedforTCRsequencing.WedescribeamethodtomatchTCR sequenceswithTcellfunctionalprofilesthatincludescellsurface markers(e.g.CD3,CD4,CD8,TIGIT,PD-1)andsecretedcytokines (e.g. IL-6, TNF-a, IFN-?). Our method uses the proprietary EnumeralsinglecellplatformforbothTcellfunctionalprofiling andisolationofsingleTcellsofinterestforTCRsequencing.Here wedemonstratethatthismethodcanbeappliedtoTcellsfrom both blood and solid tumors, including lymphocytes from a metastaticmelanomapatient. Figure1.EnumeralPlatformbasedSingleTCellSelection. Tumorinfiltratedlymphocytes(TILs)wereanalyzedatsinglecelllevel on 85,000-well Enumeral array. Each single cell was p