Curis Announces New Preclinical Data for CI-8993 at the Society for Immunotherapy of Cancer (SITC) Annual Meeting

On November 9, 2021 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported a poster presentation with new preclinical data for CI-8993, a first-in-class monoclonal antibody VISTA antagonist, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36th Annual Meeting (Press release, Curis, NOV 9, 2021, View Source [SID1234594860]).

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The investigational product CI-8993 is a fully human IgG1K monoclonal antibody that binds specifically to this immune checkpoint molecule. To assist in determining the pharmacokinetics and biodistribution of CI-8993 in patients, Dr. Fiona Scott, in collaboration with Prof. Andrew Scott, both of the Olivia Newton-John Cancer Research Institute, conducted a study aimed to develop a Zirconium-89 (89Zr)-labelled CI-8993 for PET (positron-emission tomography) imaging and quantitation, and to validate in preclinical models prior to a planned human trial.

Biodistribution was assessed by image analyses, and tissue counting, with IHC analyses performed to verify VISTA antigen expression. The abstract concluded that the study has validated 89Zr-Df-CI-8993 for specific binding to huVISTA in-vivo. A clinical trial of 89Zr-Df-CI-8993 is planned in solid tumor patients.

"We are pleased to work with the Olivia Newton-John Cancer Research Institute to further our understanding CI-8993 and VISTA biology. These findings further expand the strong foundation of preclinical data supporting CI-8993 and bring us one step closer to delivering on the promise of anti-VISTA therapy for patients with solid tumors," said James Dentzer, President and Chief Executive Officer of Curis.

Details of the presentation are as follows:
Title: Preclinical evaluation of anti-VISTA antibody CI-8993 in a syngeneic huVISTA-KI model
Presenting Author: Andrew M. Scott, MD Olivia Newton-John Cancer Research Institute, Tumour Targeting Laboratory, Melbourne, VIC, Australia
Abstract Number: 324
Abstracts will be available Tuesday, November 9, 2021, at 8:00 a.m.
Virtual ePoster presentations will be available Friday, November 12, 2021, at 7:00 a.m.

Additional meeting information can be found on the SITC (Free SITC Whitepaper) website at:
View Source

The presentations will also be available under "Posters and Presentations" in the Pipeline: CI-8993 section of the Company’s website at www.curis.com

Sensei Biotherapeutics Reports Third Quarter 2021 Results and Recent Business Highlights

On November 9, 2021 Sensei Biotherapeutics, Inc. (NASDAQ: SNSE), an immunotherapy company focused on the discovery and development of next generation therapeutics for cancer, reported financial results for the third quarter ended September 30, 2021 and provided recent corporate updates (Press release, Sensei Biotherapeutics, NOV 9, 2021, View Source [SID1234594876]).

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"In the third quarter, we witnessed rapid preclinical progress with our TMAb platform, which is designed to address the challenge of resistance to checkpoint blockade. The global PD-1/PD-L1 checkpoint inhibitor market in 2020 was valued at greater than $30 billion1, yet approximately only 20-30 percent of people respond to treatment2," said John Celebi, president and chief executive officer of Sensei Biotherapeutics. "VISTA is an immune checkpoint that is widely expressed on myeloid cells within the tumor microenvironment, a hub of immunosuppressive activity, and is implicated in resistance to checkpoint blockade. VISTA has been historically difficult to address therapeutically due to the presence of a pharmacokinetic sink in the blood and unique pH-dependent biology where the pH of the tumor is more acidic than the rest of the body. We have identified a promising first product candidate, SNS-101, by characterizing a robust set of pH-selective fully human anti-VISTA antibodies. Later this week at SITC (Free SITC Whitepaper), we plan to present preclinical data demonstrating how we rationally designed SNS-101 to block VISTA at low pH within the tumor microenvironment and present initial in vivo data with SNS-101."

Mr. Celebi continued, "We also continue to advance our ImmunoPhage platform to generate new tumor-specific T-cells and are looking forward to providing more updates when we finalize the genetic design of the new ImmunoPhage backbone. Importantly, we are well funded with more than $156 million to advance our two platforms."

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1PD-1 and PD-L1 Inhibitors Market Size In 2021 – MarketWatch, 360Research.
2 Jin-Yu Sun, Resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms, predictive factors, and future perspectives, volume 8, Biomarker Research, 2020.

Third Quarter Highlights and Pipeline Milestones:

TMAb (Tumor Microenvironment Activated Biologics) Platform

VISTA (V-domain Ig suppressor of T cell activation) is an immune checkpoint that is implicated in resistance to PD-1/PD-L1 and correlates with poor survival across numerous cancers. In the third quarter, Sensei achieved the following milestones for this program:

In August, Sensei announced it had selected SNS-101, a potent pH-dependent product candidate that selectively blocks the interaction of VISTA with its receptor, PSGL-1, in the low pH tumor microenvironment. The identification of SNS-101 was partly based on nonclinical data from a human VISTA knock-in mouse model, which showed that TMAb antibodies significantly enhanced anti-tumor responses in combination with PD-1 blockade compared to treatment with PD-1 blockade alone.
In July, Sensei selected a CDMO for the manufacture of GMP-grade material to advance its SNS-VISTA program toward clinical studies.
In September, Sensei announced that an abstract for SNS-101 was accepted for poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting being held in Washington, D.C. from November 10 – 14, 2021. Data highlighted in the poster are the first preclinical data to be presented by Sensei Bio in a scientific forum from the company’s TMAb platform.
Sensei will host a virtual science symposium on Tuesday, November 16, 2021, at 4:00 p.m. Eastern Time to discuss the potential of the VISTA checkpoint inhibitor to address current limitations of immune checkpoint therapy. The event will be hosted by Sensei’s management team and will include a presentation on VISTA biology by Robert Schreiber, Ph.D., the Andrew M. Bursky and Jane M. Bursky Distinguished Professor of Pathology and Immunology, Professor of Molecular Microbiology and co-leader of the tumor immunology program at the Siteman Comprehensive Cancer Center and Founding Director of the Center for Human Immunology and Immunotherapy Programs at the Washington University School of Medicine. A live webcast of the symposium will be available under "Events & Presentations" in the Investors section of the company’s website at www.senseibio.com. An archived replay will be available for approximately 90 days following the event.
Sensei has initiated IND-enabling studies for SNS-101. Key nonclinical studies include the generation of a broader set of in vivo efficacy data from Sensei’s human VISTA knock-in mouse models, nonclinical pharmacokinetic data, and nonclinical safety data.
VSIG4 (V-Set and Immunoglobulin Domain Containing 4) is a B7-family related protein and a potent inhibitor of T-cell activity, frequently overexpressed on tumor-associated macrophages and a potential driver of immunosuppressive macrophage polarization. VSIG4 is implicated in resistance to checkpoint blockade. Expression of VSIG4 is also found within normal tissues, presenting potential safety challenges, making VSIG4 an ideal candidate for Sensei’s TMAb platform.

Sensei has initiated its antibody discovery campaign.
Sensei plans to select a product candidate from this program in 2023.
ImmunoPhage Platform

SNS-401-NG is a potential first-in-class, multi-antigenic personalized ImmunoPhage candidate being developed in collaboration with the University of Washington designed to treat a broad range of cancers. The first proof-of concept clinical application is directed to the treatment of Merkel Cell Carcinoma (MCC), an aggressive form of skin cancer commonly driven by the Merkel Cell Polyoma Virus. Once clinical proof of concept is achieved, Sensei plans to evaluate a broader study in patients with multiple tumor types, potentially including head and neck cancer, lung cancer, melanoma, and triple negative breast cancer based on the prevalence of Phortress antigens.

Sensei is finalizing the genetic design of its next generation ImmunoPhage, which will serve as the backbone for delivery of anti-tumor antigens to the immune system.
Sensei intends to initiate IND-enabling studies for this product candidate in the second half of 2022.
Corporate

In August, Sensei strengthened its board of directors with the appointed of Kristian Humer as an independent director to its Board.
In October, the company promoted Edward van der Horst, Ph.D. to Senior Vice President, TMAb Research. The company plans to hire additional team members to extend the capabilities of its TMAb and ImmunoPhage programs.
Third Quarter 2021 Financial Results

Cash Position – Cash, cash equivalents and marketable securities were $156.7 million as of September 30, 2021, as compared to $16.6 million as of December 31, 2020. Sensei expects the current cash balance to fund operations at least into the first half of 2024.

Research and Development (R&D) Expenses – R&D expenses were $6.4 million for the quarter ended September 30, 2021, compared to $3.6 million for the quarter ended September 30, 2020. The increase in R&D expenses was primarily attributable to increased headcount to support Sensei’s research, development, and manufacturing activities.

General and Administrative (G&A) Expenses – G&A expenses were $3.9 million for the quarter ended September 30, 2021, compared to $1.8 million for the quarter ended September 30, 2020. The increase in G&A expenses was primarily attributable to higher personnel costs, including stock-based compensation expense, and costs associated with operating as a public company.

Net Loss – Net loss was $9.7 million, for the quarter ended September 30, 2021, compared to $5.4 million for the quarter ended September 30, 2020.

About SNS-101
SNS-101 is a potent, pH-dependent fully human monoclonal antibody designed to block the interaction of VISTA, a novel immune checkpoint that is expressed primarily on myeloid cells, with its receptor, PSGL-1. Selectivity is achieved because SNS-101 targets the active (i.e., protonated) VISTA present in the low pH tumor microenvironment. SNS-101 was selected based on 1) the lack of significant binding to VISTA at physiologic pH (i.e., deprotonated VISTA in the blood), and 2) its high-affinity binding to active VISTA (pH 6.0), which yielded a > 600-fold selectivity. Based on the biochemical properties of SNS-101, we anticipate tumor microenvironment selective activity for this preclinical product candidate. VISTA has been shown to be expressed in numerous tumor types, including non-small cell lung cancer (NSCLC).

Alkermes to Take Part in the Stifel Virtual Healthcare Conference

On November 9, 2021 Alkermes plc (Nasdaq: ALKS) announced today that management will participate in a fireside chat at the Stifel Virtual Healthcare Conference on Tuesday, Nov. 16, 2021 at 9:20 a.m. ET (2:20 p.m. GMT) (Press release, Alkermes, NOV 9, 2021, View Source [SID1234594892]). The presentation may be accessed under the Investors tab on www.alkermes.com and will be archived for 14 days.

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Mirati Therapeutics Announces Proposed Public Offering of Common Stock

On November 9, 2021 Mirati Therapeutics, Inc. (Nasdaq: MRTX) a clinical-stage oncology company, reported that it intends to offer and sell in an underwritten public offering $500 million of shares of its common stock (Press release, Mirati, NOV 9, 2021, View Source [SID1234594908]). In addition, Mirati expects to grant the underwriters of the offering a 30-day option to purchase up to an additional 15% of the total shares offered in the public offering at the public offering price, less the underwriting discounts and commissions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Goldman Sachs & Co. LLC, SVB Leerink LLC and Cowen and Company, LLC are acting as joint book-running managers for the proposed offering.

The securities described above are being offered pursuant to a shelf registration statement filed by Mirati with the Securities and Exchange Commission ("SEC") that became automatically effective upon filing. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, or by telephone at (866) 471-2526, or by email at [email protected]; or from SVB Leerink LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected]; or from Cowen and Company, LLC, c/o Broadridge Financial Solutions, Attention: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (833) 297-2926, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

I-Mab and ABL Bio Report Preclinical Data of 4-1BB-targeting Bispecific Antibodies at 2021 SITC

On November 9, 2021 I-Mab (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, and ABL Bio, Inc. (Kosdaq:298380, hereafter "ABL"), a clinical-stage biotech developing bispecific antibody technology for immune-oncology and neurodegenerative diseases, reported preclinical data of their 4-1BB bispecific antibodies at the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, I-Mab Biopharma, NOV 9, 2021, View Source [SID1234594924]). The new data demonstrate the unique mechanisms of action of TJ-CD4B/ABL111 and TJ-L14B/ABL503 which have resulted in localized drug action and reduced systemic toxicity, as well as sustained anti-tumor efficacy.

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Stimulation of 4-1BB is a promising therapeutic strategy for improving the current immunotherapy for multiple cancers. TJ-CD4B/ABL111 and TJ-L14B/ABL503, both jointly developed by I-Mab and ABL, are undergoing phase 1 clinical studies in the United States.

"Bispecific antibodies are rapidly recognized for their transformative potential, and our pipeline of highly-differentiated 4-1BB bispecific therapies are key components of our biologics pipeline development strategy," said Dr. Taylor Guo, Chief Scientific Officer of I-Mab. "Dose-limiting toxicities have hampered clinical development of 4-1BB targeting molecules as a drug class. The studies being presented at SITC (Free SITC Whitepaper) suggested that both our bispecific assets could have the ability to overcome this common problem, and we are confident that this differentiation places TJ-CD4B/ABL111 and TJ-L14B/ABL503 at the forefront of 4-1BB bispecific development."

"The preclinical data from this pair of bispecific molecules prove that our ‘Grabody-T’ platform effectively reduces peripheral toxicity by allowing the activation of T cells only in the tumor microenvironment," said Dr. Sang Hoon Lee, CEO of ABL Bio. "We look forward to further validating its therapeutic potential in the ongoing clinical studies and as we continue to develop 4-1BB bispecific antibodies in various cancer indications."

Key data highlights:

TJ-CD4B/ABL111

Poster title (#702): TJ-CD4B (ABL111), a Claudin18.2-targeted 4-1BB tumor engager induces potent tumor-dependent immune response without dose-limiting toxicity in preclinical studies

The preclinical studies confirmed the unique pharmacodynamic data and safety of TJ-CD4B/ABL111 in animal models and cell cultures. Analysis of the data found:

Potent, anti-tumor activity was observed with the proliferation of immune cells in the tumor microenvironment (TME) as well as an increase in memory T cells in the peripheral blood, suggesting long-term immunity against the tumor.
TJ-CD4B/ABL111 was well tolerated in non-human primates and did not induce a systemic immune response or liver toxicity up to levels of 100mg/kg.
Activation of immune pathways by TJ-CD4B/ABL111 was demonstrated by a pro-inflammatory profile and increased gamma interferon-regulated gene expression in primary human CD8+ T cells co-cultured with CLDN18.2 expressing cells.
TJ-L14B/ABL503

Poster title (#892): ABL503 (TJ-L14B), PD-L1x4-1BB bispecific antibody induces superior anti-tumor activity by PD-L1-dependent 4-1BB activation with the increase of 4-1BB+CD8+ T cells in tumor microenvironment

The preclinical study data confirms the unique mechanism of action of TJ-L14B/ABL503 and its potential to treat resistance to PD-L1 therapies. Analysis of the data found:

PD-L1-dependent stimulation of the 4-1BB signaling pathway was demonstrated in 4-1BB bioassays with PD-L1 expressing tumor cells
More potent 4-1BB activation by TJ-L14B/ABL503 was observed at higher PD-L1 expression confirming the requirement of PD-L1 on both tumor and immune cells for optimal activity. Cytokine release assays have also demonstrated minimal peripheral toxicity with TJ-L14B/ABL503
The in vivo efficacy of TJ-L14B/ABL503 was demonstrated in animal models with tumors expressing different levels of PD-L1. TJ-L14B/ABL503 showed anti-tumor efficacy across the PD-L1 levels. In particular, TJ-L14B/ABL503 demonstrated superior anti-tumor efficacy than atezolizumab in tumors with low PD-L1 expression
In vitro tumor-killing activity of TJ-L14B/ABL503 was superior compared to atezolizumab when tested in organoid system, even in organoids from atezolizumab non-responders
Pharmacodynamic changes in TILs and blood were evaluated in animal models. An increase in 4-1BB+ cells, CD8+ T cells, and effector memory T cells was observed in the TME and blood, indicating a strong and long-lasting anti-tumor immune response
Treatment with TJ-L14B/ABL503 increased MIG/CXCL9, MIP-1b/CCL4, and s4-1BB in the serum, and can potentially be used as pharmacodynamic markers in clinical trials
About TJ-CD4B/ABL111

TJ-CD4B, also known as ABL111, is a Claudin 18.2 and 4-1BB bispecific antibody capable of binding to tumor cells expressing Claudin 18.2, i.e., gastric cancer and pancreatic cancer cells, and stimulating intra-tumoral T cells by the 4-1BB arm designed to be activated only upon tumor engagement while silent elsewhere. TJ-CD4B/ABL111 effectively maintains a strong tumor binding property and anti-tumor activity attributable to a synergistic effect of both Claudin 18.2 antibody and 4-1BB antibody while it avoids or minimizes liver toxicity and systemic immunotoxicity commonly seen with 4-1BB antibodies as a drug class. Being developed under collaboration between I-Mab and ABL, TJ-CD4B/ABL111 is currently being investigated in a phase 1 clinical study in the U.S.

About TJ-L14B/ABL503

Being developed jointly with ABL, TJ-L14B/ABL503 is a differentiated PD-L1-based bispecific antibody with the PD-L1 arm as the tumor-dependent T-cell activator and the 4-1BB arm as the conditional T cell activator upon tumor engagement. Using ABL’s "Grabody-T" bispecific antibody platform technology, TJ-L14B/ABL503 stimulates 4-1BB activation only in the presence of PD-L1 expressing tumor cells to minimize the risk of off-tumor toxicity. Preclinical studies have demonstrated that the bispecific antibody shows better anti-tumor activity than equimolar doses of single agents alone or in combination. Phase 1 study in currently being conducted in the U.S.