On April 12, 2022 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing next generation cancer and infectious disease immunotherapies, reported that three presentations (one oral and two posters) further supporting the potential of its novel vaccine development capabilities and delivery platforms to develop transformational therapeutic cancer vaccines at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Gritstone Oncology, APR 12, 2022, View Source [SID1234612056]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The collective data we presented at AACR (Free AACR Whitepaper) reinforce our expertise in designing and delivering potent vaccines, and support the optimization of antigen cassette design, dose and vaccine regimen as key tools to induce differentiated immune response," said Andrew Allen, M.D., Ph.D., Co-founder, President and Chief Executive Officer of Gritstone. "Vaccines targeting neoantigens identified from common tumor driver mutations are of increasing interest, and the presentation on our ‘off-the-shelf’ candidate for KRAS-specific mutations, SLATE-KRAS, demonstrates our ability to both accurately define those targets and engineer the cassette and vaccine to optimize immune response based on those specific mutations. Early signals from our ongoing Phase 2 study presented at AACR (Free AACR Whitepaper) support the potential of SLATE-KRAS to drive stronger CD8+ T cell responses to mutant KRAS than our original candidate, SLATE v1. We look forward to further demonstrating the value of SLATE as evidence of clinical benefit builds."
Oral Presentation: Optimization of shared neoantigen vaccine design to increase vaccine potency: From bench to bedside and back
Presenter: Christine D Palmer, PhD
Key Highlights:
SLATE v1* was well-tolerated and demonstrated a favorable safety profile in all subjects dosed (n=26). Greatest activity was seen in six (6) NSCLC patients with KRASmut G12C mutations.
Gritstone subsequently developed a second, optimized product candidate (SLATE-KRAS) that exclusively includes epitopes from mutated KRAS.
SLATE-KRAS is being evaluated in the Phase 2 portion of a Phase 1/2 trial (NCT03953235), with initial data expected in the second half of 2022.
*SLATE v1 was administered in combination with Opdivo (nivolumab) and subcutaneous anti-CTLA-4 antibody Yervoy (ipilimumab). Opdivo and Yervoy are trademarks of Bristol-Myers Squibb Company.
Additional presentations at AACR (Free AACR Whitepaper) further elucidated the correlation between patient survival and circulating tumor DNA (ctDNA) in solid tumors (relevant to the company’s individualized vaccine program, GRANITE) and detailed a dose-response analysis, the results of which further support the dose-sparing potential of the company’s novel vector which is it utilizing in both oncology and infectious disease, self-amplifying mRNA (samRNA).
Karin Jooss, Ph.D., Executive Vice President, and Head of R&D added, "Clinical data from SLATE and GRANITE characterizing the optimal dosing regimen for our novel samRNA vector demonstrate more robust immune responses at lower doses, further supporting the overall potency and dose sparing potential of samRNA. The collective data we presented at AACR (Free AACR Whitepaper) has readthrough across our pipeline programs in both oncology and infectious disease, and further demonstrates Gritstone’s leadership in the field of neoantigen vaccines."
Poster Presentation: Comprehensive ctDNA monitoring provides early signal of clinical benefit with a novel personalized neoantigen directed immunotherapy for late-stage cancer patients
Presenter: Matthew Davis, PhD
Key Highlights:
Majority of neoantigens are retained in tumor even after patient receives treatment
ctDNA longitudinal monitoring enables real-time assessment of response/resistance
Molecular response elicited in four (4) of nine (9) treated subjects that correlated with prolonged progression-free survival and overall survival support clinical benefit of GRANITE in patients with advanced MSS-CRC
Poster Presentation: Lower doses of self-amplifying mRNA drive superior neoantigen-specific CD8+ T cell responses in cancer patients versus high doses
Presenter: Amy Rappaport, PhD
Key Highlights:
samRNA demonstrated a favorable safety profile at all 3 dose levels, with no evidence of increasing reactogenicity with sequential doses
Lower dose samRNA (30 μg) increased T cell and humoral responses following a ChAd prime, while higher doses of samRNA (300 μg) only maintained initial response to ChAd
Dose dependent induction of IFN⍺ in cancer patients and nonhuman primates suggest inhibitory impact of early innate immune activation
To view Gritstone’s AACR (Free AACR Whitepaper) presentations, visit ir.gritstonebio.com/investors/events.
About SLATE
Gritstone’s neoantigen-based immunotherapies are engineered to elicit a significant T-cell response (particularly CD8+ cytotoxic T cells) against mutation-derived tumor-specific neoantigens, or TSNA, that are identified by the company using its proprietary Gritstone EDGE artificial intelligence platform and tumor HLA peptide sequencing. SLATE, Gritstone’s "off-the-shelf" immunotherapy program, uses a priming adenoviral vector and self-amplifying mRNA vector to deliver a cassette of shared TSNA, representing mutated gene sequences that are found in multiple patients (such as KRAS mutations). SLATE is being evaluated in combination with immune checkpoint blockade in the Phase 2 portion of its clinical study (NCT03953235). Along with the candidates developed to date, SLATE represents the potential to develop a suite of "off-the-shelf" product candidates that target tumor-specific mutations across a number of patient populations and cancer types.