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

 

February 25, 2019

Date of Report

 

MARKER THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

 

Delaware 001-37939 45-4497941
(State or other jurisdiction of
incorporation)
(Commission File Number) (IRS Employer
Identification No.)

 

3200 Southwest Freeway

Suite 2240

Houston, Texas

  77027
(Address of principal executive offices)   (Zip Code)

 

(713) 400-6400

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 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))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter). Emerging growth company ¨

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

 

 

 

 

 

 

Item 8.01 Other Events.

 

On February 25, 2019, Marker Therapeutics, Inc. (“Marker” or the “Company”) issued a press release announcing a clinical update from four clinical trials using the Company’s multi-antigen targeted T cell (MultiTAA) therapies. The data was reviewed in oral and poster presentations at the Transplantation & Cellular Therapy (“TCT”) Meetings of the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research (“ASBMT” and “CIBMTR”) The meetings took place in Houston, Texas from February 20-24, 2019.

 

A copy of the press release is attached hereto as Exhibit 99.1 and is incorporated herein by reference.

 

As previously announced by the Company on January 15, 2019, the Center for Cell and Gene Therapy at Baylor College of Medicine presented data from four abstracts at ASBMT and CIBMTR meetings between February 20-February 23, 2019. The presentations include: (i) an oral presentation regarding Targeting Lymphomas Using Non-Engineered, Multi-Antigen-Specific T Cells; (ii) an oral presentation regarding Administering Leukemia-Directed Donor Lymphocytes to Patients with AML or MDS to Prevent or Treat Post-Allogeneic HSCT Relapse; (iii) an oral presentation regarding Adoptive T-Cell Therapy for Acute Lymphoblastic Leukemia Targeting Multiple Tumor-Associated Antigens; and (iv) a poster presentation regarding Safety and Efficacy of Multiantigen-Targeted T Cells for Multiple Myeloma. The studies describe results achieved using multi-tumor antigen specific T cells that were developed at the Baylor College of Medicine in the laboratories of Dr. Ann Leen and Dr. Juan Vera, and exclusively licensed to Marker Therapeutics, Inc. Copies of the presentation and posters are attached hereto as Exhibits 99.2, 99.3, 99.4, and 99.5, respectively. The presentations are available on Marker Therapeutics website at www.markertherapeutics.com under the caption “Recognition.”

 

The information furnished pursuant to Item 8.01 on this Form 8-K, including Exhibit 99.2, 99.3 and 99.4 and 99.5 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any other filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such a filing.

 

Item 9.01.Financial Statements and Exhibits.

 

(d) Exhibits.

 

Exhibit No. Description 
   
99.1 Press release issued on February 25, 2019.
   
99.2 2019 TCT Meeting Presentation- Targeting Lymphomas Using Non-Engineered, Multi-Antigen-Specific T Cells.*
   
99.3 2019 TCT Meeting Presentation- Administering Leukemia-Directed Donor Lymphocytes to Patients with AML or MDS to Prevent or Treat Post-Allogeneic HSCT Relapse. *
   
99.4 2019 TCT Meeting Presentation- Adoptive T-Cell Therapy for Acute Lymphoblastic Leukemia Targeting Multiple Tumor-Associated Antigens.*
   
99.5 2019 TCT Meeting Poster Presentation- Safety and Efficacy of Multiantigen-Targeted T Cells for Multiple Myeloma.*

 

*Furnished herewith.

 

 

  

SIGNATURES

 

In accordance with the requirements of the Exchange Act, the registrant caused this report to be signed on its behalf by the undersigned, thereunto duly authorized on this 25th day of February, 2019.

 

 

  MARKER THERAPEUTICS, INC.  
  (Registrant)  
       
  BY: /s/ Michael Loiacono  
    Michael Loiacono    
    Chief Accounting Officer  

 

 

 

 

 

Exhibit 99.1

 


 

Marker Therapeutics Announces Clinical Update at the Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR 2019

 

Houston, TX – February 25, 2019  – Marker Therapeutics, Inc. (NASDAQ:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, today announced updated data from four clinical trials using the Company’s multi-antigen targeted T cell (MultiTAA) therapies. The data was reviewed in oral and poster presentations at the Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR 2019 which took place in Houston, TX from February 20-24. Among the highlights, were results from an ongoing study including patients with acute myeloid leukemia (AML), which were reviewed in an oral presentation by Dr. Premal Lulla, M.B.B.S., Assistant Professor of Medicine, Baylor College of Medicine.

 

“We continue to be highly encouraged by the clinical results we’ve seen to date with our MultiTAA therapies. In AML, we believe we are seeing increasing evidence of meaningful therapeutic benefit for patients with limited treatment alternatives. Our MultiTAA therapy appears to be safe and well-tolerated with the potential to mediate a meaningful anti-tumor effect, in addition to demonstrating a compelling correlation between therapeutic responses, with superior in vivo expansion of our T cells,” said Peter L. Hoang, President & CEO of Marker Therapeutics. “Similarly, the studies ongoing in acute lymphoblastic leukemia, or ALL, lymphoma and multiple myeloma continue to demonstrate positive results, and are supportive of the data we presented at ASH in December, importantly with no additional disease relapses. Overall, this data update and our update at ASH 2018 in December collectively have increased our total reported number of patients to 78 as compared to the 57 patients we had reported as of November.”

 

AML Study Results

In Arm A of the AML study, 13 patients at Baylor College of Medicine were dosed with MultiTAA T cells as a maintenance therapy after receiving allogeneic stem cell transplant. Results demonstrated:

·11 out of 13 patients remain alive, ranging from 6 weeks to 2.5 years post-infusion. Nine of these patients have never relapsed after MultiTAA therapy and continue to remain in complete remission (CR), durable between 6 weeks to 2.5 years;
·Two patients saw local relapse in the central nervous system, but in both cases these patients were successfully treated with local therapy alone;

 

 

 

 

·One patient saw extramedullary relapse and was subsequently treated in the active disease arm (Arm B) of the trial, generating a CR that was durable for 13 months; and
·One patient relapsed 8 months after receiving MultiTAA T cells but following a second allogeneic stem cell transplant this patient remains alive in relapse 1.5 years following his initial T cell infusion.

 

In Arm B of the AML study, 6 patients suffering from active disease with relapsed/refractory (r/r) AML have been treated, with 1 patient having been treated twice for active disease with MultiTAA T cells;

·2 patients were non-responsive to MultiTAA therapy and progressed with r/r disease;
·1 patient developed a complete response (CR), which was durable for 13 months; and
·1 patient developed a partial response (PR) that enabled that patient to receive a second allogeneic stem cell transplant;
-The patient who developed a partial response saw significant tumor debulking, with circulating blasts reduced from over 50% to 15%.
·2 additional patients who did not meet partial response criteria experienced disease stabilization enabling a 2-month delay to next-line therapy
-Of these patients with disease stability, one patient was sufficiently stabilized to enable that patient to receive a second allogeneic stem cell transplant. The second transplant eliminated the patient’s MultiTAA T cells. This patient was given a second dose of MultiTAA T cells after initial disease relapse after the second transplant, but progressed to another line of therapy prior to any evaluable response assessment to the subsequent dose of MultiTAA T cells;
-The other patient who had disease stability saw significant reduction in tumor burden, with a reduction in circulating blasts from 70% prior to infusion of MultiTAA T cells, to approximately 45% circulating blasts after MultiTAA therapy.
·For patients in Arm B, overall survival ranged from 4 to 21 months after T cell infusions.

 

ALL Results

In addition to data from ongoing lymphoma and multiple myeloma trials, also presented in an oral presentation at the meeting were updated results from an ongoing study in ALL. Updates from this trial included:

 

·Patients are now up to 28 months in CCR (Continued Complete Remission);
·The only patient who has experienced relapse was a patient who displayed mixed donor/recipient chimerism after transplant, but remained in CCR for 6 months prior to relapse;

 

 

 

 

·Patients that remain in CCR have been durable for between 4 to 28 months, with a median duration of 16 months.

 

“We are very excited about the results we are seeing in our early clinical trials. For patients with r/r AML, we believe that MultiTAA therapies may produce meaningful improvements in overall survival of patients who historically have had a dire prognostic outlook,” stated Mythili Koneru, Senior Vice President of Clinical Development at Marker Therapeutics. “In adjuvant settings for patients currently in remission, I believe our early clinical results suggest that we may be providing significant additional protection against relapse and disease recurrence.”

 

About Marker Therapeutics, Inc.

Marker Therapeutics, Inc. is a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications. Marker’s cell therapy technology is based on the selective expansion of non-engineered, tumor-specific T cells that recognize tumor associated antigens (i.e. tumor targets) and kill tumor cells expressing those targets. Once infused into patients, this population of T cells attacks multiple tumor targets and acts to activate the patient’s immune system to produce broad spectrum anti-tumor activity. Because Marker does not genetically engineer its T cells, when compared to current engineered CAR-T and TCR-based approaches, its products (i) are significantly less expensive and easier to manufacture, (ii) appear to be markedly less toxic, and (iii) are associated with meaningful clinical benefit. As a result, Marker believes its portfolio of T cell therapies has a compelling therapeutic product profile, as compared to current gene-modified CAR-T and TCR-based therapies. 

Marker is also advancing a number of innovative peptide- and gene-based immuno-therapeutics for the treatment of metastatic solid tumors, including the Folate Receptor Alpha program (TPIV200) for breast and ovarian cancers and the HER2/neu program (TPIV100/110) for breast cancer, currently in Phase II clinical trials. In parallel, we are developing a proprietary DNA expression technology named PolyStart™ that can enhance the ability of the immune system to recognize and destroy diseased cells.

 
For additional information, please call toll free at (904) 862-6490 or visit: markertherapeutics.com 

To receive future press releases via email, please visit: https://markertherapeutics.com/email-alerts/ 

Follow us on Twitter @MRKRTherapeutic, or follow us on Facebook. 

 

 

 


Forward-Looking Statement Disclaimer
This release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Statements in this news release concerning the Company’s expectations, plans, business outlook or future performance, and any other statements concerning assumptions made or expectations as to any future events, conditions, performance or other matters, are “forward-looking statements”. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: our research and development activities relating to our non-engineered multi-tumor antigen specific T cell therapies; our TPIV200 and TPIV100/110 programs and our PolyStart™ program; the effectiveness of these programs or the possible range of application and potential curative effects and safety in the treatment of diseases; and, the timing and success of our clinical trials, as well as multi-tumor antigen specific T cell clinical trials conducted by our collaborators. Forward-looking statements are by their nature subject to risks, uncertainties and other factors which could cause actual results to differ materially from those stated in such statements. Such risks, uncertainties and factors include, but are not limited to the risks set forth in the Company’s most recent Form 10-K, 10-Q and other SEC filings which are available through EDGAR at www.sec.gov. The Company assumes no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. 


Contacts
Marker Therapeutics, Inc.
Aaron Santos

(904) 862-6490

investor.relations@markertherapeutics.com


Solebury Trout

Brad Miles

(646) 513-3125

bmiles@soleburytrout.com

- or -

 

Amy Bonanno
(914) 450-0349
abonanno@soleburytrout.com

  

 

 

Exhibit 99.2

 

Targeting Lymphomas Using Non - Engineered, Multi - Antigen Specific T Cells George Carrum, Premal Lulla, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Munu Bilgi, Tao Wang, Rammurti Kamble, Carlos A. Ramos, Rayne Rouce, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, Juan F. Vera and Ann M. Leen

 

 

Infusion Tumor - specific T cells Antigen Specificity Patient Adoptive T cell transfer Blood draw PBMCs

 

 

• Simultaneously target multiple TAAs • Target multiple epitopes (CD4 and CD8) within each antigen • T cells with native T cell receptor specificity (non - engineered) Our approach

 

 

MultiTAA T cells MultiTAA T cell therapy for lymphoma MAGEA4 PRAME Survivin NYESO1 SSX2

 

 

Activation DC Overlapping pepmixes PBMCs MultiTAA T cells Expansion MultiTAA - T Cell manufacture

 

 

0 20 40 60 80 100 % Positive cells MultiTAA - T Cell Phenotype n=39 CD4 CD8 CD3 DC TCM TEM NK

 

 

SFC/2x10 5 cells MultiTAA - T Cell Specificity SSX2 MAGEA4 PRAME Survivin NYESO1

 

 

% Specific Lysis Multi TAA - T Cell Autoreactivity E:T of 20:1

 

 

Any patient > 18 yrs with HL or NHL Active disease - in 2 nd or subsequent relapse - in 1 st relapse for indolent lymphoma after 1 st line therapy for relapse - in 1 st relapse if immunosuppressive chemotherapy contraindicated - primary refractory disease or persistent disease after 1 st line therapy - multiply relapsed patients in remission at a high risk of relapse - lymphoma as a second malignancy e.g. Richters After autologous or syngeneic SCT (adjuvant therapy) Clinical Trial: Eligibility Infusion of multiTAA - T cells specific for PRAME, SSX2, MAGEA4, NYESO1, Survivin

 

 

Antigen Escalation Phase = fixed dose 5x10 6 /m 2 – 2 pts/stage : Day 0: PRAME - specific T cells Day 28: PRAME and SSX - specific T cells Stage Two : Day 0: PRAME and SSX - specific T cells Day 28: PRAME/SSX/MAGE - specific T cells Stage Three : Day 0: PRAME/SSX/MAGE - specific T cells Day 28: PRAME/SSX/MAGE/NYESO1 - specific T cells Stage Four: Day 0: PRAME/SSX/MAGE/NYESO1 - specific T cells Day 28: PRAME/SSX/MAGE/NYESO1/Survivin - specific T cells Safety of MultiTAA T cells - Antigen escalation

 

 

PRAME/SSX/MAGE/NYESO1/Survivin - specific T cells : 2 - 4 pts at each level, 2 infusions 14 days apart Dose Level 1 : Day 0 and 14: 5x10 6 cells/m 2 Dose Level 2 : Day 0 and 14: 1x10 7 cells/m 2 Dose Level 3 : Day 0 and 14: 2x10 7 cells/m 2 Safety of MultiTAA T cells - Dose escalation

 

 

Clinical Trial: Treatment • 33 patients infused

 

 

Antigen escalation (n=4) Antigen escalation (n=4) Dose escalation (n=14) Dose escalation (n=11) Clinical Trial: Treatment Group B: Active lymphoma (failed prior lines) Group A: In remission • 33 patients infused

 

 

- 33 patients infused (0.5 - 2x10 7 cells/m 2 ) - 12 HL - 19 aggressive NHL (DLBCL/mantle/peripheral T) - 2 with composite lymphoma - No lymphodepletion - No adverse events Clinical Trial: Treatment

 

 

0 20 40 60 80 100 120 140 Pre Post Non - targeted antigens NYESO1 AFP Non - targeted antigens Pt1 (HL) – Clinical and Immune effects Post CTLs + radiation 0 10 20 30 40 50 60 70 80 90 Prame SSX2 MAGE A4 NYESO - 1 Survivin No pep Pre #1 wk1 wk2 Pre #2 mth3 S F C / 5 x 1 0 e 5 A B Pre T cells Post CTLs + radiation 0 10 20 30 40 50 60 70 80 90 Prame SSX2 MAGE A4 NYESO - 1 Survivin No pep Pre #1 wk1 wk2 Pre #2 mth3 S F C / 5 x 1 0 e 5 A B Post T cells SFC/2x10 5 0 10 20 30 40 50 Pre Post Targeted Antigens SSX2 PRAME Targeted antigens

 

 

0 20 40 60 80 100 120 140 160 180 200 PRE MTH3 MTH9 Survivin NYESO1 MAGEA4 SSX2 PRAME SFC/2x10 5 Pre Mth3 Mth9 Targeted antigens Non - targeted antigen Mth 3 Mth 9 Pre - Infusion 0 5 10 15 20 25 30 35 40 45 Pre Mth3 Mth9 MAGEC1 SFC/2x10 5 Pt2 (NHL) - Clinical and Immune effects

 

 

- 18 patients infused as adjuvant - 15/18 in remission (median 19 months) Clinical Outcomes – Adjuvant Clinical Outcomes – Adjuvant

 

 

Clinical Outcomes – Adjuvant ID Age/Sex Disease Prior Therapies Response to T cell therapy (duration) 1 * 39/M HL & DLBCL ABVD  RICE  ASCT CCR (>3 years) 2 * 78/F DLBCL R  RCHOP In remission (8 mo )  relapse 3 * 78/F DLBCL R  RCHOP  multiTAA T cells  R - Bendamustine CCR (>3 years) 4 * 21/M HL ABVD  Brentuximab  Nav /Gem  ASCT CCR (>4 years) 5 34/M HL ABVD  ICE  ASCT + XRT  Brentuximab In remission (12 mo )  relapse 6 54/M DLBCL RCHOP  R - EPOCH  R - DHAP  ASCT In remission (19 mo )  relapse 7 61/M DLBCL R - EPOCH  ASCT  XRT CCR (>2 years) 8 41/F HL ABVD + XRT  ICE  ASCT  XRT  Brentuximab  DHAP CCR (>4 years) 9 62/M T cell CHOP + XRT  ASCT CCR (>3 years) 10 53/M Mantle R - HyperCVAD  R - Bendamustine  R - Ibrutinib  ASCT + XRT CCR (>2 years) 11 39 not 67/M Mantle R - Bendamustine - Ara - C  ASCT CCR (>3 years) 12 65/F DLBCL R - EPOCH  ASCT CCR (>2 years) 13 35/M HL ABVD  Brentuximab +Bendamustine  ASCT  XRT CCR (> 2 years) 14 73/F DLBCL R - CHOP  XRT  ESHAP  RIE CCR (>1 year) 15 50/F DLBCL HyperCVAD  ASCT CCR (9 mo ) 16 41/M DLBCL ABVD  R - ICE  ASCT CCR (> 1 year) 17 32/F T cell ALCL CHOP  Brentuximab  Crizotinib  CD30 CAR T cells  Crizoinib CCR (9 mo ) 18 25/M HL ABVD  Brentuximab  ICE  ASCT CCR ( >1 year)

 

 

- 15 patients treated for active disease - 6 CRs; 4 SD; 5 PD Clinical Outcomes – Active disease

 

 

Clinical Outcomes – Active disease ID Age/Sex Disease Prior Therapies Response to multiTAA T cells (duration) 1 * 31/F HL ABVD  ICE  Cis - Gem  XRT  ASCT  EBV T cells  Brentuximab  Yttrium90  CART - CD30 Stable disease (5 mo)  Off study [ Revilimid (5 mo )  PD1] 2 * 55/F HL/NHL RCHOP + XRT  ICE  ASCT CR (4 mo) Died of pneumonia 3 * 38/M HL ABVD  XRT  IGEV  ESHAP  ASCT  GVD  XRT CR (>2 years ongoing) 4 * 44/F HL ABVD  ICE  ASCT  Brentuximab CR (>5 years ongoing) 5 46/M HL ABVD  ICE  ASCT + XRT  Brentuximab CR (>2 years ongoing) 6 46/F DLBCL RCHOP  GDC  ASCT CR (>3 years ongoing) 7 31/F HL ABVD  XRT  ICE  Nav /Gem  ASCT  HDACi  Brentuximab  Bendamustine  PD1i Stable disease (5 mo)  PD 8 69/M NHL EPOCH  Romidepsin  ASCT Stable disease (> 2 years) 9 54/M DLBCL RCHOP  R - ICE  ASCT Stable disease (6 mo )  PD  Started PD1i - >2 years; Alive 10 18/F HL ABVE - PC  XRT  IVBor  Brentuximab  PD1i Stable disease (9 mo )  PD 11 48/M DLBCL EPOCH - R  R - ICE  ASCT  XRT CR (>1 year) 12 49/M HL ABVD  ICE  ASCT  XRT  Brentuximab  Nivolumab  Bendamustine PD (3 mo ) 13 54/M DLBCL EPOCH - R  ICE - R  XRT  ASCT SD (9 mo ) 14 64/M DLBCL R - CHOP  Bendamustine / Rituxan  RICE  RIE  ASCT PD (9 mo ) 15 68/M DLBCL RCHOP  GDP  ASCT Stable disease (4 mo )  CD19 - CAR - T

 

 

• Safe to date • Feasible adjuvant and treatment • In vivo expansion of T cells directed to targeted antigens • Antigen/Epitope spreading • Clinical benefit Summary to date

 

 

Targeting Lymphomas Using Non - Engineered, Multi - Antigen Specific T Cells George Carrum, Premal Lulla, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Munu Bilgi, Tao Wang, Rammurti Kamble, Carlos A. Ramos, Rayne Rouce, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, Juan F. Vera and Ann M. Leen

 

 

 

Exhibit 99.3

 

Administering AML - directed DLIs to patients with AML or MDS Post - Allogeneic HSCT Relapse Premal Lulla, Swati Naik, Ifigeneia Tzannou, Shivani Mukhi, Manik Kuvalekar, Catherine Robertson, Carlos A Ramos, George Carrum, Rammurti Kamble, Jasleen Randhawa, Adrian P Gee, Bambi Grilley Malcolm K Brenner, Helen E Heslop, Juan F Vera and Ann M Leen

 

 

Acute Myeloid Leukemia 16% Koreth J et al, DeAngelo DJ JAMA 2009 20% Cured 80% Adverse risk/relapsed AML ~26,000/yr Allo - HSCT potentially curative Adverse risks >CR2 Complex cytogenetics Monosomy 7 MDS  AML t - AML MLL - r FLT3/DNMT3A etc

 

 

BMT - CTN 0901. Scott et al J Clin Oncol. 2017 Outcomes of AML patients post - alloHSCT 1 - year survival after relapse: 23% 18 month Relapse rate post - HSCT MAC - SCT 14% RIC - SCT 48% Bejanyan et al BBMT 2015

 

 

Infusion SCT recipient Cell expansion Tumor - specific T cells Antigen specificity Blood draw Donor lymphocytes Adoptive T cell transfer SCT donor

 

 

MultiTAA - T cells for AML/MDS TAA Freq. WT1 72 - 90% PRAME 40 - 60% Survivin 90 - 100% NY - ESO1 0 - 36%

 

 

• Simultaneously target multiple TAAs • Target multiple epitopes (CD4 and CD8) within each antigen • T cells with native T cell receptor specificity (non - engineered) Our approach

 

 

MultiTAA Manufacture DC Overlapping pepmixes PBMCs MultiTAA T cells

 

 

CD3+ CD4+ CD8+ RO+/ 62L+/ CCR7 - Profile of MultiTAA - T cells % Positive cells Phenotype % Specific lysis n=24 0% 5% 10% 15% 20% 25% 30% 0% 20% 40% 60% 80% 100% RO+/ 62L+/ CCR7+ RO+/ 62L - / CCR7 - Alloreactive potential

 

 

PRAME WT1 NYESO1 Survivin 0.1 1 10 100 1000 MultiTAA T cell specificity SFC/2x10 5

 

 

PRAME WT1 NYESO1 Survivin 0.1 1 10 100 1000 MultiTAA T cell specificity SFC/2x10 5 Line clones 1 10 100 1000 10000 100000 # of clones mean = 5382 clones (1697 – 16227) n=12

 

 

Any patient with AML/MDS post allo - HSCT Phase I trial - ADSPAM AML/MDS patients  30 days post allo - HSCT AML/MDS patients  30 days post allo - HSCT GROUP B – Active disease GROUP A - Adjuvant DL1 5x10 6 cells/m 2 DL2 1x10 7 cells/m 2 DL3 2x10 7 cells/m 2 Dose Escalation Donor - derived multiTAA T cells

 

 

Clinical trial: Current status 27 patients (24 AML and 3 MDS) Patients Enrolled: 20 patients (0.5 - 2x10 7 cells/m 2 ) Patients Treated: Grade II or lesser Grade III 3 (all grade I elevation in LFTs 1 grade III LFT elevation (resolved with 0.5 mg/kg prednisone)

 

 

ID Age/ G Disease Prior Treatments 1* 57/F FLT3 - ITD CIA  Sorafenib  CIAx2  RIC - SCT 2 18/F FLT3 - ITD Bortezomib / Dauno EC  sorafenib  MAC - SCT 5 55/F MLL - r 7+3  HiDAC  MAC - SCT 6 70/F AML CR3 7+3  HiDAC  CIA  RIC - SCT - Relapse  7+3 7 53/F DNMT3a 7+3  HiDAC  MAC - SCT 10 65/M MLL - r 7+3x2  5 - Azax11  RIC - SCT 11 55/M t - AML Mitoxantrone /Ara - C  RIC - SCT  Relapse  7+3 12 45/M Ph+ AML 7+3+imatinib  MAC - SCT 13 51/F AML CR2 7+3  HiDAC  Relapse  FLA  HiDAC  MAC - SCT 14 54/F Complex - rIPSS : Int - 2 5 - azax11  Transf - dep  RIC - SCT 15 58/M RAEB - 1 rIPSS : Int - 2 Decitabine  RIC - SCT  Relapse with RAEB  CIA  relapse as MDS  DLIx4 16 53/F CR2 (MRD+) 7+3  HiDAC  Relapse  FLA  MRD+  MAC - SCT 18 18/F FLT3 - ITD/MRD+ AAML1031  Relapse -- . CPX - 351  FLAG  Ara - C/Peg/ Midostaurin  refractory  Venetoclax / Decitabine  Residual disease  MAC - SCT Patients infused – ARM A

 

 

ID Disease Wk 4 Marrow (% blasts) Relapse? Status at last f/up 1* FLT3 - ITD 0 No, but bone relapse Treated on ARM B (9 mo’s post - infusion) 2 FLT3 - ITD 0 No Alive in CR (2.5 years) 5 MLL - r 0 No, CNS relapse, Local Rx alone Alive in CR (2 years) 6 AML CR3 0 No, CNS relapse Local Rx alone Alive in CR (1.5 years) 7 DNMT3a 0 No Alive in CR (1.5 years) 10 MLL - r 0 No Alive in CR (6 mo ) 11 t - AML 0 No Alive in CR (6 mo ) 12 Ph+ AML 0 No Alive in CR (9 mo ) 13 AML CR2 0 No Alive in CR (9 mo ) 14 MDS 0 No Died in CR (1 year) 15 MDS 0 Yes (8 months ) 2 nd transplant, alive in relapse (1.5 years) 16 CR2 MRD+ 0 No Alive in CR (6 mo ) 18 FLT3 - ITD/MRD+ 0 No Alive in CR (week 6) Outcomes – ARM A

 

 

ID Ag e/G Disease Prior Treatments 3 70/M IDH1 mut 7+3  decitabine  IDH inhib  cutis relapse  CIA  RIC - SCT  Relapse 4 16/M MDS  AML Double cord SCT  AML Relapse  C  haplo - SCTx2  Relapse 1* 57/F FLT3 - ITD CIA  Sorafenib  CIAx2  RIC - SCT  mTAA - T cells  steroids  Relapse 8 55/M Induc . failure 7+3  HiDAC x4  RIC - SCT  Relapse  DLIx4  MEC  5 - aza  Relapse 9 23/M Del 17p CIAx3  haplo - SCT  Relapse  CIA - decitabine  haplo - SCT  5 - aza  Nivolumab  CD123 BiTE  MEC - decitabine  midostaurin  Relapse 9* 23/M Del 17p CIAx3  haplo - SCT#1  Relapse  CIA - decitabine  haplo - SCT#2  5 - aza  Nivolumab  CD123 BiTE  MEC - decitabine  midostaurin  Relapse  mTAA T cells  haplo - SCT#3  Relapse 17 20/F FLT3 - ITD 7+3  HiDAC  MAC - SCT  Relapse  CIA  Relapse GROUP B: Active AML: 7 patients treated for active AML Patients infused – ARM B

 

 

Outcomes – ARM B ID Disease Day 0 Week 4 Response Status at last f/up 3 IDH1 mut Skin relapse Stable skin lesion NR PD (3 months)  HiDAC chemo 4 MDS  AML 30% blasts 30% NR PD (4 weeks)  Hospice (4 mo ) 1* FLT3 - ITD 4 bone lesions All resolved CR Relapse (13 mo )  7+3 chemo 8 Induc . failure 50% blasts 15% PR PR (4 mo )  2 nd donor SCT (6 mo ) 9 Del 17p 30% blasts 30% NR SD (2 mo )  Chemo/ venetoclax  Same donor SCT (6 mo ) 9* Del 17p 30% blasts N/E N/E PD (3 weeks)  Ara - C chemo 17 FLT3 - ITD 70% blasts 45% NR SD (2 mo )  chemo/ venetoclax

 

 

ID Disease Day 0 Week 4 Response Status at last f/up 3 IDH1 mut Skin relapse Stable skin lesion NR PD (3 mo )  HiDAC chemo 4 MDS  AML 30% blasts 30% NR PD (4 wks )  Hospice 1* FLT3 - ITD 4 bone lesions All resolved CR CR (13 mo )  Relapse  7+3 chemo 8 Induc . failure 50% blasts 15% PR PR (4 mo )  2 nd alloHSCT 9 Del 17p 30% blasts 30% NR SD (2 mo )  Chemo/ venetoclax  4 th alloHSCT 9* Del 17p 30% blasts N/E N/E PD (3 wks )  Ara - C chemo 17 FLT3 - ITD 70% blasts 45% NR SD (2 mo )  Chemo/ venetoclax Outcomes – ARM B

 

 

Tracking infused clones in vivo Rationale: • Infused lymphocytes are not gene modified • Leukemia specific T cell clones enriched in infused line Approach: • TCR Deep sequencing of donor - T cell product • Track expansion of line - derived clones in vivo

 

 

In vivo expansion of line clones 0.5 1 1.5 2 By week 4 Overall Fold change (from baseline) 382 line - exclusive clones 0% 20% 40% 60% Marrow n=4 Week 4 n=12 Productive Frequency 0.5% line - exclusive clones

 

 

0% 20% 40% 60% Preinfusion By week 4 By disease response Relapse/progress No relapse/progression Responders vs Non - responders 0 40 80 120 Pre Wk4 Responders Non - responders IFN γ ELISPOT %Repertoire n=3 n=4 n=9 n=7 SFC/5x10 5

 

 

Relapse Lesions - 4 FLT3mut AML received T cells as adjuvant (120 days post HSCT) Clinical course – Pt#1 SFC/5x10 5 0 2 4 6 8 10 12 14 16 pre inf 1 Week 8 Mo5 Prame NYESO1 Survivin WT1 6.1% 7% 1.8% Prednisone

 

 

Tumor – antigen expression WT1 H+E Clinical course – Pt#1

 

 

Post - T cell (Mo.11) Clinical course – Pt#1 0 5 10 15 20 Post decitabine Post - decitabine (Mo.10) 0 80 160 240 CR NYESO - 1 PRAME WT1 Survivin 0 80 160 240 Marrow • CASSSGQAYEQYF • CASSQVFPNTGELFF 1.45% 2.47% 3.07%

 

 

Clinical course – Pt#8 TAA expression % cells Intensity PRAME 50 - 75% 2+ Survivin <10% 2+ NYESO1 <10% 1+ WT1 <10% 1+ ANC SFC/5x10 5 Blasts%

 

 

Summary course - SM • Leukemia - directed donor T cell infusions are safe • Mediate anti - tumor effects • In vivo expansion superior in responders • Antigen spreading studies ongoing • Investigation of immune escape mechanisms

 

 

Administering AML - directed DLIs to patients with AML or MDS Post - Allogeneic HSCT Relapse Premal Lulla, Swati Naik, Ifigeneia Tzannou, Shivani Mukhi, Manik Kuvalekar, Catherine Robertson, Carlos A Ramos, George Carrum, Rammurti Kamble, Jasleen Randhawa, Adrian P Gee, Bambi Grilley Malcolm K Brenner, Helen E Heslop, Juan F Vera and Ann M Leen Funding : Evans MDS discovery research grant, Leukemia Texas, Leukemia and Lymphoma SCOR, Lymphoma SPORE, ASBMT New Investigator Award, ASH Scholar Award, BCM Junior Faculty Seed Funding Award, EPCRS - DLDCC, LLS/Rising Tide, ARC - Coalition

 

 

Exhibit 99.4

 

Adoptive T cell therapy for ALL targeting multiple tumor associated antigens Swati Naik, Premal Lulla, Ifigeneia Tzannou, Shivani Mukhi, Manik Kuvalekar, Catherine Robertson, George Carrum , Rammurti Kamble , Adrian P Gee, Bambi Grilley, Robert Krance , Malcolm K Brenner, Helen E Heslop, Juan F Vera, Stephen Gottschalk and Ann M Leen

 

 

Fagioli Hematologica 2013 Porter et al , BBMT 2011 Arellano, BBMT 2006 ALL Relapse after HSCT • Leukemic relapse is major cause of treatment failure after HSCT – Incidence of relapse: 24 - 35% • Poor prognosis for pts who relapse – Particularly those who relapse early post - HSCT – Overall survival: 7 - 32%

 

 

• Strategies to prevent relapse – Prophylactic use of targeted agents (e.g. TKIs) – Modulation of immune suppression • Promote immune reconstitution resulting in GvL effect – Immunotherapeutic intervention with DLIs • Enhance GvL effect Wayne, Hematology 2017 De Lima,BBMT 2013 Alyea et al, BBMT, 2010 Prevention of ALL relapse

 

 

Infusion SCT recipient Blood draw Donor lymphocytes Adoptive T cell transfer SCT donor • Low tumor - specific T cell frequency • High frequency of alloreactive cells (GvHD)

 

 

Infusion SCT recipient Cell expansion Tumor - specific T cells Antigen specificity Blood draw Donor lymphocytes Adoptive T cell transfer SCT donor

 

 

MultiTAA T cell therapy for ALL TAA Freq. WT1 70% PRAME 65% Survivin 40%

 

 

DC Pepmix spanning full length WT1, PRAME, Survivin PBMCs MultiTAA T cells Activation Expansion MultiTAA - T Cell manufacture

 

 

% Positive cells MultiTAA T cell profile CD3 CD4 CD8 CD3+/ RO+/ 62L+ CD3+/ RO+/ 62L - Phenotype n=11 -10% 0% 10% 20% 30% 40% 20:1 % Specific lysis Safety

 

 

1 10 100 1000 0 1 2 3 4 Specificity Prame Survivin WT1 SFC/2x10 5 MultiTAA T cell profile

 

 

DL1 5x10 6 cells/m 2 DL2 1x10 7 cells/m 2 DL3 2x10 7 cells/m 2 Any patient with ALL who received an allogeneic SCT from a family donor Given after day +30 post - transplant Study design (STELLA)

 

 

ID Age/G Disease Prior Treatments Dose level 1 5/F Ph + ALL Induction chemo  Primary induction failure  MRD SCT 1 2 18/F HR - ALL Completed therapy for HR - ALL  Relapse  MRD SCT 1 3 18/F Ph + ALL Completed therapy for HR - ALL  Relapse  MRDSCT  Relapse  Chemo  CD34+ top - off 1 4 41/M HR - ALL HyperCVAD + Ofatumumab x 5 cycles  MRD SCT 1 5 8/M Ph + ALL Completed therapy for HR - ALL  Relapse  MRD SCT 1 6 48/F HR - ALL Induction chemo  Primary induction failure  MRD SCT 2 9 12/F T - cell ALL Completed therapy for T - ALL  Relapse  MRD SCT 2 10 18/M HR - ALL Induction chemo  Primary induction failure  MRD SCT 2 11 12/F MPAL Induction chemotherapy  MRD SCT 3 12 16/M Ph + ALL Relapsed on therapy for HR - ALL  MRD SCT 3 n=10 Patients infused – STELLA

 

 

• No Dose Limiting Toxicities (DLTs) • No GVHD • No CRS/neurotoxicity or other adverse events • Three patients not evaluable per protocol: – received >0.5mg/kg steroids within 4 weeks of infusion – Pt 1 and 12: Stress dose steroids for sepsis – Pt 6: Steroids for elevation of AST/ALT, GVHD ruled out Safety

 

 

ID Age/G Disease Dose level Clinical course 2 18/F HR - ALL 1 CR with mixed chimerism for 6 months  Relapse 3 18/F Ph + ALL 1 Alive in CR ( 22 months post - infusion) 4 41/M HR - ALL 1 Alive in CR ( 28 months post - infusion) 5 8/M Ph + ALL 1 Died in CR ( 9 months post - infusion) 9 12/F T - cell ALL 2 Alive in CR ( 17 months post - infusion) 10 18/M HR - ALL 2 Alive in CR ( 15 months post - infusion) 11 12/F MPAL 3 Alive in CR ( 4 months post - infusion) Median follow - up 16 months (range 4 - 28 months) Clinical outcomes

 

 

SFC/5x10 5 0 50 100 150 200 250 300 350 Preinf Wk 4 WT1 Survivin Prame Pt 3 - CR 0 5 10 15 20 25 30 35 Preinf Wk 4 WT1 Survivin Prame Pt 4 - CR SFC/5x10 5 0 2 4 6 8 10 12 14 16 18 20 Preinf Wk 4 WT1 Survivin Prame Pt 2 - Relapse SFC/5x10 5 Immune Reconstitution

 

 

PRAME 4+ WT1 Pre neg Tumor antigen expression and T cell expansion SFC/5x10 5 0 50 100 150 200 250 300 350 Preinf Wk 4 WT1 Survivin Prame Pt 3 Immune Reconstitution

 

 

SFC/5x10 5 Target Antigens Antigen spreading 0 50 100 150 200 250 300 350 Preinf Wk 4 WT1 Survivin Prame 0 100 200 300 400 500 Preinf Wk 4 AFP MART1 MC1 MA3 MA2B MA1 NYESO1 mageA4 SSX2 Pt 3 Antigen Spreading

 

 

• Feasible for both B - cell and T - cell ALL • Safe to date, well - tolerated • In vivo expansion of tumor - antigen associated T - cells directed to target antigens • Evidence of antigen spreading which may contribute to relapse prevention • May present a safe and effective strategy to prevent leukemic relapse post - HSCT Summary

 

 

 

Exhibit 99.5

 

In this fashion we have now identified the HLA - restriction for four additional immuno - dominant epitopes that Conclusions Safety and efficacy of multi - TAA - T cells for Myeloma Thus, infusion of autologous multiTAA - targeted T cells directed to PRAME, SSX 2 , MAGEA 4 , NY - ESO - 1 and Survivin has been safe and provided durable clinical benefit to patients with lymphomas . Responses in all six patients who entered a CR were durable and associated with an expansion of infused T cells as well as the induction of antigen spreading . Characteristics of mTAA - T cells Figure 1 Premal Lulla , Ifigeneia Tzannou , George Carrum , Carlos A . Ramos, Rammurti Kamble , Mrinalini Bilgi , Adrian P . Gee Shivani Mukhi , Betty Chung, Ayumi Watanabe, Manik Kuvalekar , Bambi Grilley , Malcolm K . Brenner, Helen E . Heslop , Juan F . Vera and Ann M . Leen Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, and Texas Children’s Hospital, Houston, Texas, USA AL, JFV, MKB and HH are co - founders of Marker Therapeutics that aspires to commercialize the described approach to cell therapy Clinical Outcomes Responses in patients Infusion Cell expansion TAA - specific T cells Antigen Specificity Adoptive T cell transfer Blood draw T lymphocytes Lymphoma patient Despite an array of approved agents for the treatment of multiple myeloma (MM), most patients eventually relapse after conventional treatments . The adoptive transfer of tumor - targeted T cells has demonstrated efficacy in the treatment of patients with chemo - refractory hematological malignancies including MM . While the majority of T cell - based therapies in the clinic explore genetically modified T cells that target a single tumor - expressed antigen, we have developed a strategy to generate non - engineered T cell lines that simultaneously target a number of MM - expressed antigens, thereby reducing the risk of tumor immune evasion . We manufacture multiTAA - specific T cells targeting the tumor antigens PRAME, SSX 2 , MAGEA 4 , NY - ESO - 1 and Survivin ( Table 1 ) by culturing patient - derived PBMCs with DCs loaded with pepmixes spanning all 5 target antigens in the presence of a Th 1 - polarizing/pro - proliferative cytokine cocktail ( Figure 2 ) . Figure 2 - Manufacturing process Antigen Expression in lympomas Survivin 90 - 100% SSX2 35 - 61% PRAME 36 - 48% NY - ESO - 1 25 - 31% MAGE - A4 17 - 30% Table 1: Expression of TAAs on lymphoma cells Expansion 7 days Activating Cytokines Introduction Figure 4 - Specificity in an ELISPOT Assay Figure 7: Complete responses in a patient (ID:#2) with lambda light chain myeloma correlates with expansion of infused mTAA - T cells Ten patients were refractory to their latest therapy and had active MM, while 8 were in remission at the time of infusion . At the 6 week assessment, of the 10 patients infused to treat active disease, 1 had a CR, 1 had a PR and 8 had SD . Seven of these 10 patients were infused > 1 year ago . Although 2 of the 7 subsequently had disease progression, the remaining 5 continue to respond, with sustained CR ( 1 ), PR ( 2 ) or SD ( 2 ) . ( Tables 2 , 3 ) . None of the treated patients developed cytokine release syndrome, neurotoxicity or any other infusion related adverse events . To date we have infused 20 patients who had received a median of 4 lines of prior therapy at cell doses ranging from 0 . 5 - 2 x 10 7 /m 2 . 12 patients were refractory to their latest therapy and had active MM, while 8 were in remission at the time of infusion . Of the 8 patients in CR at the time of T cell infusion, all remained in CCR at the week 6 disease assessment and of the 6 evaluable patients who are > 1 year post T cells, only 1 has relapsed . Figure 5 TCR clonality We have successfully generated multi - antigen - targeted lines for 19 patients, comprising a polyclonal mixture of CD 4 + ( 28 . 9 “ 7 . 2 % ) and CD 8 + ( 56 . 6 “ 7 . 2 % ) T cells ( Figure 3 ) reactive against 2 to 5 of the target antigens ( Figure 4 ), with no activity against non - malignant autologous targets ( 2 “ 3 % specific lysis ; E : T 20 : 1 ) . We assessed the clonal diversity using TCR vβ deep sequencing analysis and found that the majority (mean 79 % ; range : 59 to 95 % ; Figure 5 ) represented rare T cell clones that were unique to the ex vivo expanded cell line, thereby enabling in vivo tracking studies . We have initiated a phase I/II clinical trial to explore the safety and efficacy of mTAA - directed T cells administered to patients with myeloma who have failed at least one line of prior therapy . The schema for enrollment is shown in Figure 6 . We have treated 20 patients (Group A : 11 , Group B : 9 ) so far : 12 with active myeloma and 8 with myeloma in at doses of 0 . 5 - 2 x 10 7 multiTAA - T cells/m 2 in 2 infusions 2 weeks apart without prior lymphodepleting chemotherapy . Table 2: Clinical outcomes of patients treated on group A Table 3: Clinical outcomes of patients treated on group B Figure 8: Immune escape in a patient (ID#3) with treatment refractory multiple myeloma Shown in Figure 7 is an example of a patient with lambda light chain myeloma with residual marrow disease despite undergoing several lines of prior therapies . Six weeks post - infusion, this patient entered a CR as measured by paraprotein levels as well as by marrow findings concomitant with an increase in the circulating frequency of TAA - (MAGE - A 4 ) - specific T cells in both the blood as well as the bone marrow . The same pattern of expansion was observed when monitoring for the T cell clones present in the infused T cell line but absent in the patient prior to infusion ( Figure 7 ) . Patient # 3 had active multiple myeloma despite recently undergoing an autologous HSCT . At baseline the patients tumor cells expressed Survivin, MAGE - A 4 and PRAME as assessed by immunohistochemistry analysis ( Figure 8 ) . Within 3 months of T cell infusion, there was an increase in the circulating frequency of T cells specific for the targeted TAAs as well as non - targeted TAAs (antigen spreading) in the blood and the bone marrow . However by month 6 the patient developed progressive disease along with loss of TAA - specific T cells within the marrow . Coincident with relapse the patients tumor lost expression of Survivin, MAGEA 4 and PRAME in the presence of circulating Survivin, PRAME and MAGE - A 4 specific T cells (Fig 8 ) . Furthermore, mRNA sequencing demonstrated an increase in immune inhibitory markers (CTLA 4 and LAG 3 ) and an upregulation of > 400 cell cycle promoters . n=19 Figure 3 - Phenotype n=19 Group B: <90 days post autologous transplant Group A: >90 days post autologous transplant or no transplant ID Age/G Prior Treatments Marrow Week 6 Response Mo 12 1 53/M Bor / Dex  ASCT 10% Unknown SD PR 6 61/M RVD  ASCT 0% 0% CCR CCR 7 44/M CyBorD  ASCT 0% 0% CCR CCR 14 47/M RVD  ASCT 0% (MRD+) 0% (MRD+) SD SD 3* 65/F RVD  ASCT  CyBorD  Carf /D  ASCT 90% 85% SD PD (2m) 13 31/F VD 4% 0% SD SD 10 69/F VD  ASCT  R  Pom / Carf /D 10% 10% SD PD (7m) 15 70/M RVD  ASCT  R - vidaza  Pom /D  ibrutinib / Carf  dinaciclib /VD  CyBorD  Daratumumab  RD - Elot  Ixa /RD 80% 80% SD PD (3m) 2* 40/M RVD  ASCT  Pom / Carf / D  ASCT  mTAA T cells 15% 15% SD SD (3m) 18 50/F VD  ASCT  Dara/VD  XRT  ASCT 0% 0% CCR CCR (8m) 20 57/M RVD  ASCT  R  VD  Pom /D  KPD  ASCT  Ixa  Dara/D 5% (0.97 g/dl) 3% (0.53 g/dl) SD SD (3m) ID Age/G Prior Treatments Marrow Week 6 Response Mo 12 2 40/M RVD  ASCT  Pom / Carf /D  ASCT 20% 0% CR CR 3 65/F RVD  ASCT  CyBorD  Carf /D  ASCT 15% 10% SD PD (6m) 5 76/M CyBorD  ASCT 20% 15% SD PR 8 57/M VTD  ASCT  Rd  Cy/ Carf /D  ASCT 0% 0% CCR CCR 9 50/F RVD  ASCT 0% 0% CCR CCR 11 53/M VD  RVD  ASCT 0% 0% CCR Relapse (7m) 12 54/M RVD/rituximab  Rd  ASCT 0% 0% CCR CCR 17 44/F VRD  KD  ASCT 0% (0.4 g/dl 0% (0.2 g/dl) PR PR (6m) 19 70/M XRT  VD  ASCT  R  VD  KPD  ASCT 0% 0% CCR CCR (6m) Clinical responses correlated with the emergence and persistence (> 6 mths) of “line - exclusive” tumor - reactive T cells in patient peripheral blood ( Figure 6 A ) and marrow ( 6 B ), as assessed by TCR deep sequencing . The expansion of product - derived clones was higher among patients with active MM than those in remission ( 6 A ) . This matched the pattern of expansion of TAA - directed T cells as measured by an IFN - Υ ELISPOT assay ( 6 C & D ) Figure 6 T cell expansion/persistence