On October 1, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported that one oral and four poster presentations for the Company’s induced pluripotent stem cell (iPSC) product platform were accepted for presentation at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 10-14, 2021 (Press release, Fate Therapeutics, OCT 1, 2021, View Source [SID1234590638]).

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The oral presentation will highlight preclinical data for FT536, the Company’s off-the-shelf, multiplexed-engineered, iPSC-derived, chimeric antigen receptor (CAR) NK cell product candidate that uniquely targets the α3 domain of the MHC class I related proteins A (MICA) and B (MICB). In a recent publication in Cancer Immunology Research (DOI: 10.1158/2326-6066.CIR-19-0483), Kai W. Wucherpfennig, M.D., Ph.D., Chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and co-leader of the Cancer Immunology Program at Dana-Farber / Harvard Cancer Center, demonstrated that cancers with loss of MHC Class I expression can be effectively targeted with MICA/B α3 domain-specific antibodies to restore NK cell-mediated immunity against solid tumors. The FT536 program is supported by an exclusive license from the Dana-Farber Cancer Institute to intellectual property covering novel antibody fragments binding MICA/B for iPSC-derived cellular therapeutics. The Company expects to submit an Investigational New Drug (IND) application for FT536 in the fourth quarter of 2021 for the treatment of advanced solid tumors, including in combination with monoclonal antibody therapy.

Poster presentations at SITC (Free SITC Whitepaper) will include preclinical data on new functional elements that the Company is evaluating for incorporation into its iPSC-derived cell product candidates for solid tumors. These synthetic features include engineered chemokine receptors, which the Company has demonstrated can enhance the trafficking and homing of iPSC-derived CAR T cells to tumors, and synthetic TGFβ re-direct receptors, which the Company has shown can exploit immuno-suppressive cytokines found in the tumor microenvironment to potentiate iPSC-derived CAR T cells and improve anti-tumor activity.

Oral Presentation

FT536 Path to IND: Ubiquitous targeting of solid tumors with an off-the-shelf, first-of-kind MICA/B-specific CAR-iNK cellular immunotherapy
Abstract #: 117
Session 212: Cellular Therapies; November 13, 3:40 pm – 4:55 pm EST
Poster Presentation

Synthetic re-direction of TGFβ receptors as a novel strategy to enhance the anti-tumor activity of iPSC-derived CAR-T cells in solid tumors
Abstract #: 138
Chemokine receptor engineering enhances trafficking and homing of primary and iPSC-derived CAR-T cells to solid tumors
Abstract #: 120
Off-the-shelf, engineered iPSC-derived NK cells mediate potent cytotoxic activity against primary glioblastoma cells and promote durable long-term survival in vivo
Abstract #: 169
Novel FcyR recombinant fusion facilitates antibody arming of engineered iPSC-derived NK cells to enhance targeting and killing of ovarian cancer cells
Abstract #: 197
About MICA and MICB Proteins
The major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB) are induced by cellular stress, damage or transformation, and the expression of MICA and MICB proteins has been reported for many tumor types. Cytotoxic lymphocytes, such as NK cells and CD8+ T cells, can detect and bind the membrane-distal α1 and α2 domains of MICA/B, activating a potent cytotoxic response. However, cancer cells frequently evade immune cell recognition by proteolytic shedding of the α1 and α2 domains of MICA/B. The clinical importance of proteolytic shedding is reflected in the association of high serum concentrations of shed MICA/B with disease progression in many solid tumors. Several recent publications have shown that therapeutic antibodies targeting the membrane-proximal α3 domain strongly inhibited MICA/B shedding, resulting in a substantial increase in the cell surface density of MICA/B and restoration of NK cell-mediated tumor immunity (DOI:10.1126/science.aao0505). Therapeutic approaches aimed at targeting the α3 domain of MICA/B therefore represent a potentially promising novel strategy to overcome this prominent evasion mechanism as a means of restoring anti-tumor immunity.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

On October 1, 2021 Replimune Group, Inc. (Nasdaq: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported four poster presentations at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting being held November 10-14, 2021 (Press release, Replimune, OCT 1, 2021, View Source [SID1234590636]).

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Details of Replimune’s poster presentations:

Abstract Title: A phase 1 clinical trial of RP2, an enhanced potency oncolytic HSV expressing an anti-CTLA-4 antibody, as a single agent and combined with nivolumab in patients with advanced solid tumors
Abstract Number: 507
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Abstract Title: ARTACUS: An open-label, multicenter, phase 1b/2 study of RP1 in solid organ transplant recipients with advanced cutaneous malignancies (Trial in Progress presentation)
Abstract Number: 550
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Abstract Title: CERPASS: A randomized, controlled, open-label, phase 2 study of cemiplimab ± RP1 in patients with advanced cutaneous squamous cell carcinoma (Trial in Progress presentation)
Abstract Number: 547
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Abstract Title: IGNYTE: An open-label, multicenter, phase 1/2 (Ph 1/2) clinical trial of RP1 ± nivolumab in patients with advanced solid tumors (Trial in Progress presentation)
Abstract Number: 506
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

The full posters will be posted to the presentations section of the Replimune website at View Source

On October 1, 2021 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing potentially first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, reported the acceptance of a presentation on TPST-1495, a selective antagonist of both EP2 and EP4 prostaglandin receptors, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting taking place November 10-14, 2021 at the Walter E. Washington Convention Center in Washington, D.C (Press release, Tempest Therapeutics, OCT 1, 2021, View Source [SID1234590635]).

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Details of the poster presentation are as follows:

Title: Dual blockade of the EP2 and EP4 PGE2 receptors with TPST-1495 is an optimal approach for drugging the prostaglandin pathway
Abstract #: 850
Category: Novel Single Agent Immunotherapies
Date/time: 11/12/2021 – 11/13/2021, 7:00 am – 8:30 pm ET
Location: Poster Hall
To view the abstract details, please visit the SITC (Free SITC Whitepaper) 2021 website located at View Source

About TPST-1495

TPST-1495 is an orally-available small molecule designed to block the EP2 and EP4 receptors in the prostaglandin (PGE2) pathway, while sparing the homologous but differentially active EP1 and EP3 receptors. PGE2 signaling through EP2 and EP4 has been observed both to enhance tumor progression and promote immune suppression. Tempest has conducted head-to-head preclinical studies comparing TPST-1495 to single antagonists of EP2 and EP4 and observed significantly enhanced activity of TPST-1495 in both overcoming PGE2-mediated suppression of human immune cells in vitro, as well as significantly increased anti-tumor activity in mouse models of human colorectal cancer. Tempest is currently evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and possible anti-tumor activity of TPST-1495 in a multicenter Phase 1a/1b dose and schedule optimization study in subjects with advanced solid tumors, with the potential to expand in indications known to be prostaglandin-driven, including colorectal cancer, or CRC, and in a tumor indication-agnostic, biomarker-selected cohort.

On October 1, 2021 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts evaluating several investigational therapies and technologies in the company’s solid tumor product pipeline will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36thAnnual Meeting (SITC 2021), being held in Washington, DC, and virtually, November 10-14 (Press release, Genmab, OCT 1, 2021, View Source [SID1234590634]). The presentations will include a mini-oral session featuring the results of the first-in-human (FIH) phase 1/2 trial evaluating the safety and initial clinical activity of the investigational bispecific antibody, DuoBody-CD40×4-1BB (GEN1042), in patients with advanced solid tumors. Data from another FIH phase 1/2a trial, evaluating the investigational bispecific antibody, DuoBody-PD-L1×4-1BB (GEN1046) in patients with advanced solid tumors, will be presented as a poster. In addition, four posters will be presented, including one evaluating DuoBody-CD3xB7H4 (GEN1047), an investigational therapy in Genmab’s early-stage solid tumor product pipeline.

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All the abstract titles have been published on the SITC (Free SITC Whitepaper) website and may be accessed online via the SITC (Free SITC Whitepaper) Annual Meeting website. Full abstracts will be posted on November 9, 2021, at 8:00 a.m. ET.

GEN1046 and GEN1042 are being co-developed by Genmab and BioNTech (NASDAQ: BNTX) under an agreement in which the companies share all costs and future profits on a 50:50 basis.

"We are excited to present the results of these important clinical and pre-clinical studies to show the progression of the innovative technologies and investigational medicines in our antibody product pipeline and to demonstrate our commitment to delivering new therapeutic options to patients," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "While most of these studies have been conducted in the beginning stages of the clinical evaluation process, we are encouraged by the early results and look forward to seeing further results from ongoing clinical trials."

Abstracts accepted for presentation at SITC (Free SITC Whitepaper) 2021:

DuoBody-CD40×4-1BB (GEN1042):

First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody-CD40×4-1BB (GEN1042) in patients with advanced solid tumors

DuoBody-PD-L1×4-1BB (GEN1046):

Peripheral and tumoral immune activity in the expansion part of the first-in human DuoBody-PD-L1×4-1BB (GEN1046) trial
Dose selection for DuoBody-PD-L1×4-1BB (GEN1046) using a semi-mechanistic pharmacokinetics/pharmacodynamics model that leverages preclinical and clinical data
DuoBody-CD3xB7H4 (GEN1047):

In vitro and in vivo studies establish DuoBody-CD3xB7H4 as a novel drug candidate for the treatment of solid cancers

New Research and Technologies:

A scalable deep learning framework for rapid automated annotation of histologic and morphologic features from large unlabeled pan-cancer H&E datasets
A translational approach to catalog pancreatic cancer heterogeneity using spatial genomics in large patient cohorts to empower target validation and rational combination selection
Molecular characterization of AXL in solid tumor malignancies using real-world data

About DuoBody-PD-L1×4-1BB (GEN1046)
DuoBody-PD-L1x4-1BB (GEN1046) is a proprietary bispecific antibody, jointly owned by Genmab and BioNTech, created using Genmab’s DuoBody technology. It targets PD-L1 and 4-1BB, selected to block the inhibitory PD1/PD-L1 axis and simultaneously conditionally activate essential co-stimulatory activity via 4-1BB using an inert DuoBody antibody format. Two clinical studies (NCT03917381, NCT04937153) in solid tumors are ongoing. DuoBody-PD-L1x4-1BB is being co-developed by Genmab and BioNTech under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

About DuoBody-CD40×4-1BB (GEN1042)
DuoBody-CD40x4-1BB (GEN1042) is a proprietary bispecific antibody, jointly owned by Genmab and BioNTech, created using Genmab’s DuoBody technology. CD40 and 4-1BB were selected as targets to enhance both dendritic cell (DC) and antigen-dependent T-cell activation, using an inert DuoBody format. A Phase 1/2 clinical study (NCT04083599) of DuoBody-CD40x4-1BB in solid tumors is ongoing. DuoBody-CD40x4-1BB is being co-developed by Genmab and BioNTech under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

On October 1, 2021, Cue Biopharma, Inc., a Delaware corporation (the "Company"), reported that it entered into an Open Market Sale Agreement (the "Sales Agreement") with Jefferies LLC, as agent (the "Agent"), pursuant to which the Company may offer and sell shares of its common stock, $0.001 par value per share, having an aggregate offering price of up to $80,000,000 (the "Shares") from time to time through the Agent (the "Offering") (Filing, 8-K, Cue Biopharma, OCT 1, 2021, View Source [SID1234590633]). The Company is filing a prospectus supplement with the Securities and Exchange Commission (the "SEC") in connection with the Offering (the "Prospectus Supplement") under the Company’s existing shelf Registration Statement on Form S-3 (File No. 333-239357), as amended by Post-Effective Amendment No. 3, which became effective on May 21, 2021 (the "Registration Statement").

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Upon delivery of a placement notice to the Agent and subject to the terms and conditions of the Sales Agreement, the Agent may sell the Shares by any method that is deemed to be an "at the market offering" as defined in Rule 415(a)(4) under the Securities Act of 1933, as amended, including sales made directly on or through the Nasdaq Capital Market or on any other existing trading market for the Company’s common stock.

The Company or the Agent may suspend or terminate the offering of Shares upon notice to the other party, subject to certain conditions. The Agent will act as sales agent on a commercially reasonable efforts basis consistent with its normal sales and trading practices.

The Company has agreed to pay the Agent commissions for its services of acting as agent of 3.0% of the gross proceeds from the sale of the Shares pursuant to the Sales Agreement. The Company has also agreed to provide the Agent with customary indemnification and contribution rights.

A copy of the Sales Agreement is attached as Exhibit 1.1 hereto and is incorporated herein by reference. The foregoing description of the material terms of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to such exhibit.

Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Company, has issued a legal opinion relating to the Shares. A copy of such legal opinion, including the consent included therein, is attached as Exhibit 5.1 hereto.

The Shares will be sold pursuant to the Registration Statement, and offerings of the Shares will be made only by means of the Prospectus Supplement. This Current Report on Form 8-K shall not constitute an offer to sell or solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities law of such state or jurisdiction.