On April 10, 2021 Sumitomo Dainippon Pharma Oncology, Inc., a clinical-stage company focused on research and development for novel cancer therapeutics, reported new findings on a range of investigational agents from the company’s pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I, taking place April 10-15, 2021 (Press release, Sumitomo Dainippon Pharma, APR 10, 2021, View Source [SID1234577874]).

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The data presented at the meeting include preclinical and Phase 1 clinical data evaluating the potential anti-cancer activity of the PKM2 activator TP-1454, PIM inhibitor TP-3654, TNK1 inhibitor TP-5809 and CDK9 inhibitor alvocidib. Additionally, Sumitomo Dainippon Pharma Co., Ltd., the parent company of Sumitomo Dainippon Pharma Oncology (SDP Oncology), presented findings from preclinical studies of DSP-0509, a TLR7 agonist.

"As we advance our investigational agents, we are pleased to present the latest research on our diverse pipeline to the scientific community at the AACR (Free AACR Whitepaper) Virtual Annual Meeting," said Patricia S. Andrews, CEO and Global Head of Oncology, SDP Oncology. "These data reflect our relentless commitment to propelling drug discovery in oncology and our progress in advancing research in hematologic and solid malignancies."

Below are the details for the presentations:

Abstract Title

Details

Presenter

PKM2 Activation Modulates the Tumor-Immune Microenvironment and Enhances Response to Checkpoint Inhibitors in Preclinical Solid Tumor Models

Abstract #606

Saturday, April 10 at 8:30 a.m. ET

E-Poster Presentation

Salah Sommakia, Ph.D.

Sumitomo Dainippon Pharma Oncology, Inc.

Pharmacodynamic Biomarkers for Pim Inhibition with TP-3654 in Patients with Solid Tumors

Abstract #1345

Saturday, April 10 at 8:30 a.m. ET

E-Poster Presentation

Curtis A. Allred, Ph.D.

Sumitomo Dainippon Pharma Oncology, Inc.

TP-5809, a Novel TNK1 Inhibitor, Suppresses TNK1 Dependent Signaling and Tumor Growth in a Preclinical Model of Hodgkin’s Lymphoma

Abstract #1478

Saturday, April 10 at 8:30 a.m. ET

E-Poster Presentation

Tetyana V. Forostyan, Ph.D.

Sumitomo Dainippon Pharma Oncology, Inc.

CDK9 Inhibition Combined with Hypomethylating Agents Target MCL-1 Dependency in MDS and AML

Abstract #1959

Saturday, April 10 at 8:30 a.m. ET

E-Poster Presentation

Yuta Matsumura, Ph.D.

Sumitomo Dainippon Pharma Oncology, Inc.

Modulation of Immune Suppressive Cells by Toll-Like 7 Agonist DSP-0509 which Leads to Potentiate Anti-Tumor Activity of Radiotherapy

Abstract #523

Saturday, April 10 at 8:30 a.m. ET

E-Poster Presentation

Yosuke Ota, Ph.D.

Sumitomo Dainippon Pharma Co., Ltd.

About TP-1454

TP-1454 is an investigational oral pyruvate kinase M2 isoform (PKM2) activator, that is currently being evaluated in a Phase 1/1b study in patients with advanced metastatic or progressive solid tumors (NCT04328740). TP-1454 is the first PKM2 activator to be evaluated in cancer patients. Pyruvate kinase is the enzyme responsible for catalyzing the last step of glycolysis. PKM2 plays a critical role in the metabolic changes observed in cancer and immune cells and establishes a metabolic advantage for tumor cells over the tumor immune microenvironment.1

About TP-3654

TP-3654 is an investigational second-generation selective PIM kinase inhibitor under evaluation in a Phase 1 study in patients with myelofibrosis (NCT04176198), as well as a Phase 1 study in patients with advanced solid tumors (NCT03715504).

About TP-5809

TP-5809 is an investigational TNK1 inhibitor currently being evaluated in the preclinical setting.

About Alvocidib

Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in the ongoing Phase 2 Zella 202 study in patients with acute myeloid leukemia (AML) who have either relapsed from or are refractory to venetoclax in combination with azacitidine or decitabine (NCT03969420). Alvocidib is also being evaluated in Zella 102, a Phase 1b/2 study in patients with myelodysplastic syndromes (MDS) in combination with azacitidine or decitabine (NCT03593915).

About DSP-0509

DSP-0509 is an investigational synthetic Toll-like receptor (TLR) 7 agonist. In preclinical models, DSP-0509 was shown to promote the cytokine induction and cytotoxic T lymphocyte (CTL) activation mediated by agonistic effect of TLR 7 expressed in plasmacytoid dendritic cells. DSP-0509 is hypothesized to sustain the immune-mediated anticancer activity by induction of immune system memory cells and is currently being evaluated in a Phase 1 clinical trial (NCT03416335) in patients with advanced solid tumors.

About Sumitomo Dainippon Pharma Oncology

Sumitomo Dainippon Pharma Oncology, Inc., is a wholly owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd. As a global oncology organization with teams in the U.S. and Japan, SDP Oncology is relentlessly committed to advancing purposeful science by transforming new discoveries into meaningful treatments for patients with cancer. The company’s robust and diverse pipeline of preclinical and advanced-stage assets spans multiple areas, including oncogenic pathways, survival mechanisms and novel protein interactions, which aim to address unmet clinical needs in oncology.

On April 10, 2021 Gracell Biotechnologies Inc. (NASDAQ: GRCL) ("Gracell"), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported long-term follow-up data on their TruUCAR-enabled allogeneic product candidate GC027 for the treatment of adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) in an e-poster presentation at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 10 (Press release, Gracell Biotechnologies, APR 10, 2021, View Source [SID1234577873]).

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TruUCAR-enabled GC027 is a first-in-human, off-the-shelf allogeneic CAR-T stand-alone therapy targeting CD7. An ongoing, multi-center investigator-initiated Phase 1 trial in China is evaluating the safety and efficacy of GC027 for the treatment of adults with r/r T-ALL. We first reported results as oral presentation at the AACR (Free AACR Whitepaper) 2020 Annual Meeting.

The updated data with a February 4, 2021 data cut-off represents long-term follow-up as well as additional patients treated. Patients had received a median of six prior lines of therapy and received a single infusion of TruUCAR GC027 in one of three dose levels: 0.6x107cells/kg, 1.0x107cells/kg or 1.5x107cells/kg. Six patients (100%) treated achieved a complete remission with or without complete blood count recovery (CR/CRi) and five of the six patients (83%) achieved minimum residual disease negative complete remission (MRD- CR). At 6 months post treatment, three out of five patients (60%) had maintained MRD- CR. After 18.5 months of follow up for the initial patients treated, one patient continued to be MRD- CR at 16.8 months. One patient maintained MRD- CR until 9 months and one patient with primary refractory disease (no response to VDP) maintained his MRD- CR status until month 7. One additional patient treated presented initially with a high tumor burden and extensive extramedullary (EM) disease. After treatment with GC027 and as confirmed by PET CT scan, all EM lesions resolved. The patient achieved MRD- CR at day 28.

All six patients tolerated a single infusion of TruUCAR GC027. No neurotoxicity events (ICANS) or acute graft-versus-host disease (aGvHD) were observed. Cytokine release syndrome (CRS) occurred in all patients and was managed with standard of care including Tocilizumab. Overall safety findings were consistent with previous observations.

"These data show promising long-term follow-up results in r/r T-ALL patients who have very limited treatment options available," commented Dr. Martina Sersch, M.D., Chief Medical Officer of Gracell. "With these findings, GC027 may have the potential to be developed as a single-infusion stand-alone allogeneic CAR-T therapy. We are looking forward to expediting the clinical development of our TruUCAR-enabled GC027 globally, as well as expanding into additional indications beyond T-ALL."

Presentation link: View Source
Abstract link: View Source!/9325/presentation/4633

About GC027
TruUCAR-enabled GC027 is a first-in-human, off-the-shelf allogeneic CAR-T therapy targeting CD7, currently being developed for the treatment of T-ALL in adults. GC027 is manufactured from T cells of human leukocyte antigen (HLA) unmatched healthy donors. Developed on our proprietary TruUCAR platform, GC027 utilizes dual-function CAR to specifically target a patient’s own T cells and natural killer (NK) cells that would otherwise be directed against the foreign, or allogeneic, CAR-T cells resulting in rejection by the patients. This novel design allows this allogeneic cell therapy to survive a patient’s immune system without the need for combination treatment with additional potent immunosuppressant and represents a differentiated monotherapy approach.

About T-ALL
T cell malignancies are a group of cancers involving T lymphocytes, including acute T cell lymphoblastic leukemia or T-ALL. Standard of care treatment for T-ALL includes chemotherapy, radiation therapy and stem cell transplantation. Standard chemotherapy regimens only result in 30% – 40% response rate with 6 months median Overall Survival among responders. Patients with T cell malignancies usually have high relapse and mortality rates. Relapsed patients have dismal prognosis with very limited treatment options and <10% of patients surviving beyond 5 years. Due to shared common surface antigens and potential contamination by malignant cells, development of CAR-T cell therapies for T-ALL is lagged behind. In addition, no new therapies have been approved for the treatment of T-ALL since the approval of Nelarabine (marketed by GlaxoSmithKline) by the FDA in 2005. Globally, approximately 64,000 patients are diagnosed with ALL every year with over approximately 6,000 expected to be diagnosed in the United States in 2020. T-ALL accounts for approximately 25% of ALL diagnoses in adults. 1

About TruUCAR
TruUCAR is Gracell’s proprietary technology platform and is designed to generate high-quality allogeneic CAR-T cell therapies that can be administered "off-the-shelf" at lower cost and with greater convenience. With differentiated design enabled by gene editing, TruUCAR is designed to control host vs graft rejection (HvG) as well as graft vs host disease (GvHD) without the need of being co-administered with immunosuppressive drugs.

The lead program of TruUCAR platform, GC027, is manufactured using T cells from non-HLA matched healthy donors. The TruUCAR platform utilizes novel designs of a dual-function CAR or dual-CAR to reduce HvG, eliminating the need of combination therapy with additional potent immunosuppressant to induce deeper immune suppression and enabling stand-alone allogeneic CAR-T cell therapy.

On April 10, 2021 Jubilant Therapeutics Inc., a biopharmaceutical company advancing oral, small molecule modulators to address unmet medical needs in oncology and autoimmune diseases, reported that preclinical data from two programs evaluating the company’s PRMT5 inhibitor and PD-L1 inhibitor as anti-cancer agents, will be presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting taking place virtually from April 10-15, 2021 (Press release, Jubilant Therapeutics, APR 10, 2021, View Source [SID1234577872]).

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"We are excited to announce these important data from our PRMT5 and our PD-L1 programs that show efficacy and tolerability in preclinical models," said Syed Kazmi, President and Chief Executive Officer of Jubilant Therapeutics Inc. "Our oral PRMT5 inhibitor has good plasma and sustained brain exposure which results in strong target inhibition, tumor growth delay and survival advantage in both xenografts and orthotopic brain models. Our oral anti-PDL1 immunotherapeutics, with a shorter half-life, are an attractive alternative to current intravenous antibody therapies especially in the maintenance settings with potential to limit immune-mediated toxicities and side effects via innovative dosing approaches, while maintaining the class-based wide anti-tumor efficacy. We look forward to continuing our work on these programs as we see great potential for treating multiple cancers."

A link to the e-posters, listed below, is available through the AACR (Free AACR Whitepaper) website.

Title: Novel, small molecule PRMT5 inhibitors for treatment of cancer
Poster Number: 1128
Date and Time: April 10, 2021 at 8:30 a.m. Eastern Daylight Time (EDT)
Session Title: Epigenetic Targets
Presenter: Dhanalakshmi Sivanandhan, et al.

Title: Novel, small molecule inhibitors of PD-L1/PD-1 interaction
Poster Number: 1630
Date and Time: April 10, 2021 at 8:30 a.m. Eastern Daylight Time (EDT)
Session Title: Immune Checkpoints
Presenter: Dhanalakshmi Sivanandhan, et al.

PRMT5 over-expression, shown in several cancers including lymphoid, lung, breast, glioblastoma, gastric etc., is thought to be an important factor in its tumorigenicity due to its repressive function on tumor suppressor gene expression. Key highlights from an evaluation which examined the tumor growth inhibition of PRMT5 inhibitor JBI-778 in multiple cancer cell lines as well as glioblastoma, include the following:

JBI-778 is a potent PRMT5 inhibitor that is selective against other PRMTs;
JBI-778 shows potent anti-proliferative activity against a number of cancers;
This oral small molecule demonstrated anti-tumor efficacy in a Mantle Cell lymphoma model with an ED50 of < 10 mg/Kg and a complete tumor growth inhibition (97%) at a dose of 50mg/kg; and
JBI-778 exhibited sustained brain exposure and significant tumor growth inhibition in an orthotopic glioblastoma model, translating into substantial survival advantage.
JBI-778 is currently being evaluated for the treatment of multiple cancers and IND-enabling studies have commenced.

PD-L1 expression is an immune evasion mechanism exploited by many cancers, such as melanoma, non-small cell lung cancer and breast cancer, which permits cancer progression and metastasis. Key highlights from the PD-L1/PD-1 study which examined the ability of JBI-1527 to inhibit PD-L1 and restore T-cell proliferation and function, include the following:

JBI-1527 is a potent, selective inhibitor of PD-L1 which induces dimerization of the protein thereby alleviating PD-L1-induced suppression of T cell activation;
The inhibitor shows similar modulation of cytokines as Pembrolizumab in BioMAP assay and competes with anti-PD-L1 blocking antibody suggesting similar binding site on PD-L1; and
In CT-26 and MC38-hPD-L1 syngeneic models, the small molecule showed strong tumor growth inhibition comparable to anti-PD-L1 mAb/Atezolizumab, and was well tolerated.
Studies to further assess JBI-1527 and additional compounds are underway.

Jubilant Therapeutics Inc. is developing a pipeline of novel, differentiated therapeutic assets; for partnership opportunity inquiries please contact [email protected].

On April 10, 2021 Ultimovacs ASA ("Ultimovacs", ticker ULTI), reported that it is presenting a poster today on the trial design of its ongoing Phase II INITIUM clinical study evaluating nivolumab and ipilimumab in combination with the Company’s proprietary universal cancer vaccine, UV1, as first line treatment in patients with metastatic malignant melanoma, at the 2021 AACR (Free AACR Whitepaper) Annual Meeting, held virtually from April 9 to April 14, 2021 (Press release, Ultimovacs, APR 10, 2021, View Source [SID1234577869]).

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The poster, titled, "Nivolumab and ipilimumab +/- UV1 vaccine as 1st line treatment in patients with malignant melanoma (INITIUM-trial)", details the INITIUM study, a randomized, open label study investigating the efficacy and safety of UV1 vaccination in combination with nivolumab and ipilimumab as first line treatment in histologically confirmed unresectable metastatic melanoma patients. The INITIUM study is enrolling 154 patients, randomly assigned to the experimental arm or the control arm. Patients in the experimental arm will receive 8 UV1 vaccinations over 4 cycles of nivolumab and ipilimumab, whereas patients in the control arm will receive 4 cycles of nivolumab and ipilimumab without UV1 vaccination. In both arms, patients will start maintenance therapy with nivolumab after the last dose of induction therapy and will be followed until the end of the study. The primary outcome of the study is the Progression Free Survival (PFS) of patients in the experimental arm compared to patients in the control arm. Secondary outcomes include the comparison of Overall Survival (OS) and Objective Response Rate (ORR) between the groups.

Details of the presentation are as follows:

Title:

Nivolumab and ipilimumab +/- UV1 vaccine as 1st line treatment in patients with malignant melanoma (INITIUM-trial)

Session Type:

E-poster Session

Session Title:

Phase II Clinical Trials in Progress

Abstract Number:

CT23

The poster is available on Ultimovacs’ corporate website at www.ultimovacs.com.

On April 10, 2021 Guardant Health, Inc. (Nasdaq: GH), along with leading academic institutions and pharmaceutical companies, reported new data at the AACR (Free AACR Whitepaper) Virtual Annual Meeting I, April 10-15, 2021, highlighting the use of the company’s proprietary blood tests to advance precision oncology (Press release, Guardant Health, APR 10, 2021, View Source [SID1234577868]).

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Key findings demonstrate the value of Guardant360, Guardant360 CDx, and GuardantOMNI liquid biopsy tests to detect clinically actionable mutations, inform treatment for patients as their cancer progresses, and reveal tumor evolution and resistance in response to interventional therapies, including immunotherapies.

"At this year’s AACR (Free AACR Whitepaper), we highlight the growing clinical utility of our liquid biopsy tests, from revealing critical genomic and molecular insights that contribute to vitally important drug development efforts, to further informing treatment decisions as patients with advanced disease progress," said Helmy Eltoukhy, Guardant Health CEO. "As we exit the pandemic, the ability to effectively treat advanced cancers that may have remained undetected during the past year will be critical, and there is no room for error or further delays in finding the right treatment or clinical trial. Now more than ever, our liquid biopsies are needed to accelerate the accessibility of effective treatment options for patients most in need of precise clinical therapies."

Guardant360 CDx validated for use with Amgen’s investigational KRASG12C inhibitor, sotorasib

Data from the phase 2 CodeBreaK 100 trial evaluating investigational sotorasib in patients with advanced non-small cell lung cancer (NSCLC) showed the objective response rate was comparable in patients selected using Guardant360 CDx liquid biopsy or tissue biopsy, with high concordance demonstrated between the two assays.

"The study results highlight that the Guardant360 blood-based companion diagnostic test was effective at selecting patients with KRAS G12C who may benefit from treatment with sotorasib, said Darryl Sleep, senior vice president, global medical and chief medical officer, Amgen. "KRAS G12C can only be detected with a biomarker test and with one in eight patients with NSCLC harboring the KRAS G12C mutation, there is a critical need to improve access to high quality diagnostics and more routine screening."

Title

Clinical validation of plasma cell-free DNA (cfDNA) sequencing in the phase 2 trial of sotorasib in patients (pts) with KRAS p.G12C mutated NSCLC

Abstract No.

CT181

Session

Phase II Clinical Trials

Date / Time

e-Poster Presentation: April 10, 2021, 8:30 AM – 11:59 PM EDT

Guardant360 CDx delivers results at low inputs, which can potentially increase patient samples for clinical decision-making and clinical studies

Study shows Guardant360 CDx provides comprehensive tumor profiling results with robust analytical performance at demonstrated low inputs (5ng cutoff). These data suggest that Guardant360 CDx has the potential to guide therapy decisions for about 34% more patients compared to some liquid biopsies that use 2 blood collection tubes (BCT) for minimal 30ng of cell-free DNA (cfDNA). The data also show that the ability to process samples below 15ng input from a single BCT increases the yield of EGFR driver mutations by >25%. Furthermore, because retrospective studies are often performed with as little as 2mL of plasma, the study shows that the Guardant360 CDx is expected to return valid results on over 88% of such samples, which may be outside the performance specifications for other assays.

Title

The liquid biopsy Guardant360 CDx has robust performance at low inputs allowing for high rate of returning patient results

Abstract No.

572

Session

Liquid Biopsies: Circulating DNA

Date / Time

April 10, 2021, 8:30 AM – 11:59 PM EDT

Studies show Guardant360 provides early indication of treatment response and resistance mechanisms in the management of advanced cancer

Data presented are consistent with prior studies, across various treatments and indications,1-10 showing Guardant360 provides early indication of treatment response and clinical outcomes by measuring molecular response or changes to circulating tumor DNA from baseline at different time-points. In addition, data presented show that Guardant360 can also reveal tumor evolution and resistance in response to interventional therapies, including immunotherapies.

Title

Reversion patterns in homologous recombination repair genes in metastatic cancer patients profiled by cell-free DNA

Abstract No.

25

Session

Biomarkers

Date / Time

MINISYMPOSIUM PRESENTATION
April 10, 2021, 2:20 PM – 2:30 PM EDT

Title

Comparison of molecular response calculations for prediction of patient outcome

Abstract No.

401

Session

Biomarkers Predictive of Therapeutic Benefit

Date / Time

Poster presentation: April 10, 2021, 8:30 AM – 11:59 PM EDT

Other abstracts and poster presentations

Title

Confirmation of Target Inhibition and Anti-Tumor Activity of the SHP2 Inhibitor RMC-4630 via Longitudinal Analysis of ctDNA in RAS-Addicted Tumors in a Phase 1 Clinical Study

Title

A single institution experience with Guardant360 liquid biopsy for therapeutic decision in advanced solid tumors

Title

NTRK1 fusion detection from clinical cfDNA NGS using a de novo fusion caller

Title

Detection of somatic copy number alterations from on-target and off-target sequencing data