Document



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): May 12, 2020
_______________________________________
https://cdn.kscope.io/32e8cdbe3396d0709e17f0fe2c2dc4cd-genocealogosmall1a01.jpg
GENOCEA BIOSCIENCES, INC.
(Exact name of registrant as specified in its charter)
_______________________________________
Delaware
 
001-36289
 
51-0596811
(State or other jurisdiction of
incorporation)
 
(Commission File Number)
 
(IRS Employer
Identification No.)
 
Cambridge Discovery Park
100 Acorn Park Drive, 5th Floor
Cambridge, MA 02140
(Address of principal executive offices, including zip code)
(Registrant’s telephone number, including area code): (617) 876-8191
_______________________________________
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:
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:
Title of each class

 
Trading symbol(s)

 
Name of each exchange on which registered

Common stock, $0.001 par value per share

 
GNCA
 
NASDAQ Capital Market

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-2of the Securities Exchange Act of 1934 (§ 240 12b-2 of this chapter).

Emerging Growth Company o

If an emerging growth company, indicate by a 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. o


1



Item 7.01 Regulation FD Disclosure.
 
On May 12, 2020, Genocea Biosciences (the “Company”) hosted a Virtual Key Opinion Leader ("KOL") Symposium on GEN-011. A copy of the presentation is attached to this Current Report on Form 8-K as Exhibit 99.1 and is incorporated herein by reference. The presentation will also be available online at http://ir.genocea.com/events-and-presentations as of May 12, 2020; however, the Company’s website and any information contained on the website are not incorporated herein.

The information responsive to Item 7.01 of this Form 8-K, including Exhibit 99.1, 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 in any filing under the Securities Act of 1933, as amended, 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
99.1
 

 





2



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.
 
 
 
GENOCEA BIOSCIENCES, INC.
 
 
 
 
By:
/s/ DIANTHA DUVALL
 
 
Diantha Duvall
 
 
Chief Financial Officer
 
 
(Principal Financial Officer)
 
Date: May 12, 2020
 



 




3
gen011kolsymposium12may2
GEN-011: Transforming T cell therapy for solid tumors KOL Symposium 12 May 2020


 
GEN-011: Designed to improve upon TIL therapy T cells targeting the right tumor neoantigens Peripheral blood T cells enabling greater activity and durability Robust and rapidly scalable manufacturing process 2


 
TIL therapy: Current gold standard for solid tumor cell therapy Tumor-infiltrating lymphocyte (TIL) 2,3,4 CAR-T therapy Unproven in solid tumors TCR-transduced (TCR-T) Limited clinical validation HLA-limited Durable efficacy Potential safety concerns1 in checkpoint-refractory patients 1. Linette et al., Blood (2013) 3. Sarnaik et al., ASCO Annual Meeting (2019) 2. Goff et al., JCO (2016) 4. Jazaeri et al., ASCO Annual Meeting (2019) 3


 
Lessons learned: Drivers of TIL therapy clinical success Target multiple tumor neoantigens • Amplify existing anti-tumor T cell responses • More neoantigens combats tumor heterogeneity, limits tumor escape Deploy both CD4+ and CD8+ T cells • CD4+ T cells provide critical support to CD8+ T cells CD4+ CD8+ • Both CD4+ and CD8+ T cells can kill tumor Exploit TCR diversity • Ensures product is HLA-agnostic, to work for any patient • Provides multiple T cell “shots on goal” to target every neoantigen Minimize off-tumor effects for patient safety • Non-engineered patient T cells targeting tumor-specific neoantigens; CAR-T and TCR-T approaches have faced challenges 4


 
GEN-011 – a new category of neoantigen T cell therapy: Peripheral blood-derived, ATLAS™-powered Peripheral blood (leukopak) GEN-011 Up to 30 neoantigens Neoantigen-specific cell expansion in fully closed single-use vessels Autologous, non-engineered 5


 
GEN-011: Embraces TIL advantages, overcomes limitations TIL limitations GEN-011 GEN-011 advantages Neoantigen • Targets up to 30 relevant neoantigens with selection via + + • Limited tumor specificity CD4 and CD8 memory T cells • Cannot avoid inhibitory, • Avoids pro-tumor Inhibigens™ that may be detrimental to clinical response pro-tumor responses • No extra surgery, or viable tumor, required • Requires sterile resection of tumors with sufficient T cells Peripheral blood • Billions of T cells to relevant tumor lymphocytes (PBLs) neoantigens, with proven cytolytic capacity • Expansion protocols exacerbate already exhausted TIL • Non-exhausted cells with potential for superior activity and persistence 6


 
Neoantigen selection with 7


 
ATLAS empirically selects the relevant neoantigens of tumor-specific T cell responses Comprehensive identification of Tumor NGS Unique Bacterial vectors biopsy analysis plasmids for expressing each Autologous patient- and every candidate dendritic cell tumor-relevant T candidate cell responses neoantigen • Multiplexed cytokine readout Autologous • CD4+ and CD8+ T T cell cell responses Blood sample • Identify Inhibigens 8


 
ATLAS enables identification of neoantigens to which CD8+ and CD4+ T cells appropriately respond CD8+ T cells CD4+ T cells Neoantigens Background responses Concentration Concentration   IFN IFN Inhibigens Normalized to Background Control Background Normalized to Control Background Normalized to Individual mutations Individual mutations Example: NSCLC patient; 52 mutations identified and profiled; IFN responses shown • ATLAS neoantigens are ideal immunotherapy targets: tumor specific, surface-presented and immunogenic • Inhibitory neoantigens (Inhibigens) downregulate anti-tumor cytokine responses and should be excluded • No relationship between TMB, expression levels, or truncal mutations and productive neoantigen profiles 9


 
Identification and exclusion of Inhibigens is critical for cancer immunotherapies 1,600 Adjuvant only 1,000 Adjuvant only ) 1,400 Protective vaccine ) 3 3 Inhibigens + Adjuvant m Protective vaccine + Inhibigen m 800 1,200 m ( m ( e 1,000 e 600 m m u l u 800 l o v o v r 400 600 o r o m u 400 m T u 200 T 200 0 0 0 6 8 10 12 14 16 18 0 3 6 8 10 12 14 16 18 20 22 24 Day Day Therapeutic mouse vaccination with a pool of ATLAS-identified The presence of Inhibigens in an otherwise protective mouse Inhibigens drives tumor hyperprogression vaccine completely abrogates protection • Inhibigen-specific T cells may be responsible for hyperprogression after checkpoint blockade therapy1,2 Experiments run in B16F10 melanoma model 1. Champiat et al., Clin Can Res (2017) 2. Ferrara et al., JAMA (2018) 10


 
GEN-011 manufacturing process and drug product profile 11


 
GEN-011 uses peripheral blood T cells T cells from PBL are readily accessible, non-exhausted, and contain relevant neoantigen specificities TIL limitations Recent landmark publications demonstrate the relevance of PBLs • Incomplete coverage of Antigen Experienced T Cells from Peripheral Blood tumor neoantigens Recognize p53 Neoantigens Clonal replacement of tumor-specific T cells following PD-1 blockade • Requires sterile resection of Prospective identification of neoantigen- specific lymphocytes in the peripheral blood Peripheral T cell expansion predicts tumor infiltration tumors with sufficient T cells of melanoma patients and clinical response (significant time and cost) Immunological ignorance is an enabling feature of the oligo- Late-differentiated effector neoantigen- clonal T cell response to melanoma neoantigens • Expansion protocols specific CD8+ T cells are enriched in peripheral blood of non-small cell lung exacerbate already carcinoma patients responding to exhausted TIL atezolizumab treatment Efficient identification of neoantigen-specific Sensitive and frequent identification of high avidity T cell responses in advanced human ovarian neo-epitope specific CD8+ T cells in immunotherapy- cancer naive ovarian cancer 12


 
Robust and rapidly scalable manufacturing process with fully closed single-use technology Peripheral blood Phenotypic cell sort (leukopak) GEN-011 Process Peripheral blood ensures starting cell material T cells rapidly obtained from every patient, dramatically expanding accessible patient population Up to 30 verified Robust process designed to deliver billions of neoantigens cells for every patient Up to 20-day expansion of neoantigen-specific Rapidly expandable manufacturing capacity cells in fully closed with low capital investment single-use GRex Monocyte- vessels derived dendritic cells Cost and delivery time of therapy expected to be highly favorable as compared to TILs 13


 
GEN-011 delivers billions of neoantigen-specific T cells Contains an average of Majority of T cells are specific for 3.3 billion T cells ATLAS-identified neoantigens 1010 Irrelevant antigens Neoantigens CD8+ 65% r e 5% b + m CD4 u 9 n 10 l l e c T Activation Marker 2 Marker Activation 2 Marker Activation 108 Pre-expansion cells GEN-011 Activation Marker 1 Activation Marker 1 Mean across development runs with cancer patient and healthy donor material 14


 
GEN-011 exhibits unparalleled breadth of neoantigen coverage GEN-011 targets up to 30 neoantigens Recent selected TIL data show successful amplification to only 89% 4% of antigens included in the process1 Recent conventional TIL data show responses to an average of 6% of the predicted neoantigens2 GEN-011 T cells are specific for 89% Recent engineered TCR-T data suggest only up to three of all intended neoantigen targets* neoantigen specificities targeted3 *Mean across development runs with cancer patient material 1. Samuel et al., AACR Presentation (April 2020) 3. Cristea et al., 2020 AACR Presentation (April 2020) 2. Creelan et al., AACR Presentation (April 2020) 15


 
GEN-011 T cells are highly functional and cytotoxic An average of 16,000 cells per T cells are potently million are secreting cytokines in cytolytic against target response to stimulation neoantigens CD8+ 100 Specific Neoantigens + 80 CD4 Unpulsed Control y t i c i 60 Negative x o t control o t y 40 C % 20 0 16:1 8:1 4:1 2:1 1:1 0.5:1 Neoantigen Effector:Target ratio pool 16


 
PBL-derived T cells exhibit greater neoantigen activity and potency compared to TIL T cells are activated appropriately Neoantigen-specific T cells upon neoantigen stimulation secrete abundant IFN + 80 CD8 25000 n o i t a l u 20000 g 60 e r p L u r 15000 m / e g k r 40 p a  m N 10000 F n I o i t a 20 v i t 5000 c A % 0 0 1 GEN-011 TIL GEN-011 TIL2 Squares = healthy donor, viral antigen 1. Chandran Lancet 2017; Stevanovic JCO 2015; n=25 Circles = cancer patients, neoantigens 2. Ritthipichai, SITC 2017 poster N=5 17


 
GEN-011: CD4+ and CD8+ memory T cells for anti-tumor efficacy, persistence and proliferation Pure T cell drug product Desired T cell memory phenotype Non-T cells 100 1% CD8+ y 75 c 35% n e u q 50 e CD4+ r F 65% T cells % 25 99% 0 Naive Terminal Memory memory (Cm+Em) (TEMRA) Data represent mean across cancer patients and healthy donor development runs 18


 
GEN-011: Embraces TIL advantages, overcomes limitations TIL limitations GEN-011 GEN-011 advantages Neoantigen • Targets up to 30 relevant neoantigens with selection via + + • Limited tumor specificity CD4 and CD8 memory T cells • Cannot avoid inhibitory, • Avoids pro-tumor Inhibigens™ that may be detrimental to clinical response pro-tumor responses • No extra surgery, or viable tumor, required • Requires sterile resection of tumors with sufficient T cells Peripheral blood • Billions of T cells to relevant tumor lymphocytes (PBLs) neoantigens, with proven cytolytic capacity • Expansion protocols exacerbate already exhausted TIL • Non-exhausted cells with potential for superior activity and persistence 19


 
Clinical Development 20


 
Trial Objectives Phase 1/2 pilot study of GEN-011 in refractory solid tumors Targeted Indications Cohort A Trial Objectives Melanoma, NSCLC, SCLC, Multiple low dose • Safety SCCHN, UC, RCC, SqCC skin, (up to12 patients) • Clinical activity SqCCAC • No lymphodepletion • ORR • Low dose IL-2 Tumors responsive to • DOR immunotherapy or virally- • GEN-011 proliferation associated without available and persistence disease control Cohort B • Tumor T cell penetration Single high dose (up to12 patients) • Lymphodepletion • High dose IL-2 IND this quarter - Preliminary clinical data in 1H 2021 21


 
GEN-011: Transforming neoantigen T cell therapy for solid tumors T cells targeting the right tumor neoantigens Peripheral blood T cells enabling greater activity and durability Robust and rapidly scalable manufacturing process 22