On October 31, 2023 Chimeric Therapeutics (ASX:CHM, "Chimeric" or the "Company"), an Australian leader in cell therapy, reported that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of CHM 2101, Chimeric’s first in class CDH17 CAR T cell therapy for gastrointestinal cancers (Press release, Chimeric Therapeutics, OCT 31, 2023, View Source [SID1234636521]).

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The company plans to investigate CHM 2101 in a multi center, open label Phase 1A/B clinical trial for patients with advanced Colorectal Cancer, Gastric Cancer and Neuroendocrine Tumours. CHM 2101 is a 3rd generation, novel CDH17 CAR T cell therapy that targets CDH17, a cancer target associated with poor prognosis and metastasis in the most common gastrointestinal tumors including Colorectal Cancer, Gastric Cancer and Neuroendocrine Tumours.

The clinical program for CHM 2101 builds upon the preclinical studies published in the preeminent scientific journal, Nature Cancer in March 2022 by leading immunotherapy scientist Xianxin Hua, MD, PhD, and his team at the Abramson Family Cancer Research Institute at the University of Pennsylvania. These experiments demonstrated that CHM 2101 was able to eradicate established tumours in seven cancer models with no toxicity to normal tissues.

"It is exciting to see the advancement from discovery of the CDH17 target and CAR T therapy in preclinical studies to the initiation of clinical trials in patients with GI-cancers and neuroendocrine tumors," said Xianxin Hua, MD, PhD, Professor of Cancer Biology in Penn’s Perelman School of Medicine, an investigator at the Abramson Family Cancer Research Institute and a Harrington Scholar Innovator. "This is a critical step forward in developing an entirely new CAR T therapy for GI-cancers and neuroendocrine tumors, providing new hopes for the cancer patients who are refractory to the existing therapies."

With the FDA IND clearance Chimeric will now begin the initiation of a phase 1 /2 multi-site clinical trial in patients with advanced Colorectal Cancer, Gastric Cancer and Neuroendocrine Tumours. The study is planned to begin patient enrollment in 2024. (ClinicalTrials.gov ID: NCT06055439)

"I am really excited about the planned Phase 1 clinical trial of CHM 2101 and the opportunity to bring a potentially transformative new investigational agent to cancer patients who need them most," said Michael R. Bishop, MD, Professor of Medicine and Director, The David and Etta Jonas Center for Cellular Therapy, University of Chicago.

On October 31, 2023 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that pre-clinical data on MUC1-CAR T-cells to overcome key challenges of targeting solid tumors, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 38th Annual Meeting (SITC 2023), that will take place on November 1-5, 2023 at San Diego Convention Center in San Diego (CA) (Press release, Cellectis, OCT 31, 2023, View Source [SID1234636520]).

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The data will be presented by Laurent Poirot, Ph.D., SVP Immunology of Cellectis, in a poster session that will be held November 4th 2023 from 9:00 a.m. to 8:30 p.m. PDT, at San Diego Convention Center, Hall A.

The poster is number 254 and it is entitled "TGF-Beta Blockade Combined with Activation-Induced IL12 Secretion Synergize to Optimize Potency of MUC1-CAR T-cells in Preclinical Targeting of Triple-Negative Breast Cancer".

While during SITC (Free SITC Whitepaper) 2022 Cellectis presented how TALEN-mediated gene editing allows programming of various functions addressing both safety and potency aspects of allogenic CAR T-cell therapy, this year the company’s presentation will focus on the synergistic benefits of ΔPD1-IL12 and TGFBR2-KO attributes in preclinical models of triple negative breast cancer.

"We demonstrate that combination of the ΔPD1-IL12 with TGFBR2 KO not only enhanced CAR-T cell activity but surprisingly limit their accumulation outside the tumor, therefore reducing the risks of off-tumor toxicity. These cells also show strong anti-tumor activity against distal tumors when infused intratumorally.", said Laurent Poirot, Ph.D., SVP Immunology at Cellectis.

These pre-clinical data highlight the capability of multi-armored allogeneic CAR T-cells to preserve their activity despite the immunosuppressive microenvironment, while mitigating potential safety concerns.

On October 31, 2023 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported that it will present data updates across multiple immuno-oncology programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s ("SITC") 38th Annual Meeting in San Diego, USA, from November 1-5, 2023 (Press release, BioNTech, OCT 31, 2023, View Source [SID1234636519]). The updates will feature one oral and four poster presentations for the investigational anti-CTLA-4 monoclonal antibody candidate BNT316/ONC-392 (gotistobart), the FixVac off-the-shelf mRNA cancer vaccine BNT116, the ex-vivo T cell therapy BNT221, and the two bi-specific antibodies BNT312/GEN1042 and BNT313/GEN1053.

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Highlights of BioNTech’s clinical stage programs to be presented at SITC (Free SITC Whitepaper) Annual Meeting 2023:

BioNTech will share new Phase 1/2 (NCT04140526) data of its next-generation anti-CTLA-4 monoclonal antibody candidate BNT316/ONC-392 (gotistobart) in non-small cell lung cancer ("NSCLC") patients that progressed on anti-PD-1/PD-L1 therapy. The candidate is being jointly developed with OncoC4, Inc. ("OncoC4"). The results show encouraging anti-tumor activity for BNT316/ONC-392 as monotherapy in patients with immuno-oncologic (IO)-resistant NSCLC, as well as a manageable safety profile.
First clinical data will be presented on the LuCa-MERIT-1 Phase 1 study (NCT05142189) with BioNTech’s off-the-shelf mRNA therapeutic cancer vaccine candidate BNT116 alone and in combination with cemiplimab in patients with advanced, unresectable, or metastatic NSCLC. The data show encouraging initial clinical activity in heavily pre-treated patients with advanced NSCLC and a tolerable safety profile.
As a follow-up to the data recently presented at ESMO (Free ESMO Whitepaper), BioNTech will give an update on the first-in-human Phase 1 study with BNT221 (NCT04625205), a personalized, autologous neoantigen-specific T cell therapy, which is being evaluated in patients with anti-PD-1- and anti-CTLA-4-pretreated advanced or metastatic melanoma. The data update includes nine patients. Seven of these patients have stable disease with shrinkage of tumor lesions in four of these patients. The initial results show a manageable safety profile with no dose limiting toxicities. In addition, preliminary translational data show multiple functional neoantigen-specific T cell responses in all evaluable patients.
BioNTech has established a diversified clinical oncology pipeline of more than 25 programs in high unmet medical need solid tumor indications in more than 30 clinical studies, including seven programs in advanced Phase 2 studies and one candidate in a pivotal Phase 3 study. BioNTech is advancing the Company’s key programs into late-stage development while strengthening its clinical-stage oncology pipeline with synergistic potential, with the aim to deliver the next generation of oncology breakthroughs.

The full abstracts are available on the SITC (Free SITC Whitepaper) Annual Meeting website. Click here for further information on BioNTech’s pipeline candidates.

Full Presentation Details:

Oral Presentation
Candidate: BNT316/ONC-392 (gotistobart)
Session Title: Promising Novel Biotechnologies for the Next Wave of IO Innovation
Abstract Title: "Single-agent safety and activities of target-preserving anti-CTLA-4 antibody gotistobart (ONC-392/BNT316) in PD-(L)1 resistant metastatic NSCLC and population PK analysis in patients with solid tumors"
Abstract Number: 599
Date: Friday, November 3, 2023
Time: 3:30-5:10 PM PDT

Poster Presentations
Candidate: BNT116
Abstract Title: "Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen RNA vaccine BNT116 in patients with advanced non-small cell lung cancer"
Abstract Number: 597
Date: Friday, November 3, 2023, and Saturday, November 4, 2023

Candidate: BNT221
Abstract Title: "Interim clinical and translational data from NTC-001, a phase I study to evaluate the non-engineered neoantigen-specific T cell product BNT221 in patients with advanced or metastatic" melanoma
Abstract Number: 769
Date: Saturday, November 4, 2023

Candidate: BNT312/GEN1042
Abstract Title: "GEN1042-mIgG2a, an Fc-inert mouse-human chimeric variant of GEN1042 (DuoBody-CD40x4-1BB), exhibits in vivo antitumor activity and peripheral immune modulation"
Abstract Number: 1181
Date: Friday, November 3, 2023

Candidate: BNT313/GEN1053
Abstract Title: "Combination of HexaBody-CD27 with PD-(L)1 blockade potentiates single-agent activity leading to enhanced human T-cell effector functions in vitro"
Abstract Number: 813
Date: Friday, November 3, 2023

On October 31, 2023 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a global clinical-stage biopharmaceutical company focused on using a groundbreaking technology platform for drug discovery and developing innovative therapies to improve clinical outcomes for patients with high unmet medical needs, reported that the Company and Professor Kathryn M. Eisenmann of the University of Toledo College of Medicine presented a poster on the potent efficacy of plinabulin in a derived patient model of glioblastoma, a disease of high unmet need at the 2023 AACR (Free AACR Whitepaper) Special Conference in Cancer Research: Brain Cancer on Oct 20th, 2023 at Minneapolis, MN (Press release, BeyondSpring Pharmaceuticals, OCT 31, 2023, View Source;utm_medium=rss&utm_campaign=beyondspring-and-professor-k-eisenmann-of-the-university-of-toledo-college-of-medicine-present-poster-highlighting-plinabulins-anti-cancer-efficacy-in-primary-and-recurrent-glioblastoma-pati [SID1234636518]). Professor Eisenmann’s research interests include glioblastoma invasion programs and developing small molecule therapeutics that target cytoskeleton networks. She has built a comprehensive glioblastoma patient cell line repository of more than 6 dozen samples of primary and therapy-resistant recurrent tumors.

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The presentation demonstrated the monotherapy activity of plinabulin at 10-30 nM at killing 3D neurospheres from five glioblastoma multiforme (GBM) patient-derived primary cell lines and therapy-resistant cell lines. Plinabulin was confirmed to have anti-proliferative properties in GBM at therapeutic concentrations. Plinabulin blocked GBM patient-derived sphere invasion, while significantly decreasing GBM cell survival and extension of microtubules. This model is directly relevant to the recurrence of glioblastoma after resection, and plinabulin killed these cells and stopped the spread of the tumor.

"Recent investigation into targeted therapies has failed to address invasion and cytoskeleton based GBM therapy resistance. Plinabulin, which can pass blood brain barrier, is a differentiated microtubule-targeting and immune-oncology agent. Plinabulin had shown single agent activity in transgenic GBM animal model with survival benefit compared to placebo," said Dr. Kathryn Eisenmann. "This presentation further demonstrates plinabulin’s potential in brain tumor, which is severely unmet medical needs."

On October 31, 2023 Be Biopharma, Inc. ("Be Bio"), a company pioneering the discovery and development of Engineered B Cell Medicines (BCMs), reported that it will present preclinical data demonstrating that a BCM-derived biologic can deliver steady-state plasma concentrations of a bispecific T cell engager at clinically relevant doses for treatment of relapsed/refractory acute lymphoblastic leukemia (ALL) (Press release, Be Biopharma, OCT 31, 2023, View Source [SID1234636517]). Findings from the study, conducted jointly with researchers at Seattle Children’s Research Institute, will be presented during the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 38th Annual Meeting.

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"These findings underscore the clinical potential of BCMs as an emerging platform for sustained delivery of antitumor biologics. Our platform enables production of a diverse set of therapeutic proteins, including those difficult to manufacture using traditional systems, and offers a promising approach for a new class of medicines with broad therapeutic utility," said Dr. Rick Morgan, Chief Scientific Officer, Be Bio.

"Bispecific T cell engagers are highly effective in treating relapsed/refractory ALL; however, their short half-life requires continuous intravenous administration at high doses for four-week increments. This study demonstrates that engineered plasma cells can deliver a constant infusion of bispecific T cell engagers at a steady-state, clinically relevant plasma concentration, offering a potential therapeutic advance to decrease the burden of therapy for patients," said Dr. Richard James, principal investigator at Seattle Children’s Research Institute.

The poster presentation details are as follows:

Saturday, November 4, 2023, 12:10 pm PDT

Session: Session 205a: Rapid Oral Abstract-Basic Science

Title: "Development of ex vivo precision gene engineered B cell medicines that produce highly active and sustained levels of transgenic anti-tumor biologics"

Lead Authors: Rick Morgan, Ph.D., and Richard G. James, Ph.D.

Presenter: Sean Arlauckas, Ph.D., Director, Oncology Research, Be Bio

Abstract #: 409

Bispecific T cell engagers, consisting of an anti-CD3 single-chain fragment variable (scFv) fused to an anti-tumor antigen scFv, are highly effective in the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). However, the short half-life of bispecific T cell engagers necessitates continuous intravenous administration at high doses for four weeks at a time. Given their ability to produce proteins at steady state, BCMs are particularly well-suited to overcome these pharmacokinetic shortcomings. To generate BCMs, B cells are engineered ex vivo to constitutively secrete transgenic biologics and then differentiated into plasma cells. These cells were chosen for their high antibody production capacity (thousands of Ig molecules/cell/sec) and ability to engraft without preconditioning, making them a highly attractive cell-based platform for continuous biologic delivery1.

About the Study

To demonstrate proof-of-concept, a transgene coding for a bispecific anti-CD3:CD19 scFv was integrated into a safe-harbor locus of primary human B cells via targeted gene knock in. The engineered B cells were then differentiated into plasma cells ex vivo. Assessment of in vivo anti-tumor activity of these BCMs was conducted in NSG mice harboring a patient-derived CD19-expressing xenograft (PDx). Mice were inoculated with a luciferized B-ALL PDx line and autologous T cells were delivered after tumor transfer. Significant reduction in tumor burden (bioluminescent flux, area under the curve) was observed over the course of the 17-day study in the anti-CD3:CD19 scFv cohort compared to controls, which was in concordance with heightened in vivo T cell activation. The ~1000 pg/mL bispecific T cell engagers detected in mouse plasma demonstrated that a BCM-derived biologic can meet or even exceed the steady-state plasma concentrations achieved with clinically relevant blinatumomab doses2.

Deidentified human PBMCs were acquired under informed consent from the Fred Hutch Specimen Processing and Research Cell Bank (protocol #3942).

No toxicities were identified in this study.

About Engineered B Cell Medicines – A New Class of Cellular Medicines

Imagine what could "Be?" In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs). BCMs have the potential to be durable, allogeneic, redosable and administered without toxic conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.