Sanofi completes acquisition of Kadmon

On November 9, 2021 Sanofi reported the completion of its acquisition of Kadmon Holdings, Inc. The acquisition further strengthens growth and expansion for the General Medicines portfolio (Press release, Sanofi, NOV 9, 2021, View Source [SID1234594879]).

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Shareholders of Kadmon common stock voted to approve the acquisition at a special meeting of stockholders on November 5, 2021 and will receive $9.50 per share in cash, which represents a total equity value of approximately $1.9 billion (on a fully diluted basis).

Sanofi completed its acquisition of Kadmon through the merger of a wholly owned subsidiary of Sanofi with and into Kadmon, pursuant to Section 251 of the General Corporation Law of the State of Delaware, with Kadmon continuing as the surviving corporation and becoming an indirect, wholly owned subsidiary of Sanofi.

As of November 9, 2021, Kadmon common stock will cease to be traded on the NASDAQ Global Select Stock Market and will be subsequently deregistered.

Centerview Partners acted as exclusive financial advisor to Sanofi while Weil, Gotshal & Manges LLP acted as legal counsel to Sanofi. Cantor Fitzgerald & Co. and Moelis & Company LLC acted as exclusive financial advisors to Kadmon in the transaction, while DLA Piper LLP (US) acted as legal counsel. H.C. Wainwright & Co., LLC acted as capital markets advisor to Kadmon management.

Fate Therapeutics Announces Abstract Highlighting FT538 and FT573 Programs Selected for Presentation at SITC 2021 Annual Meeting Press Conference

On November 9, 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 the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Communications Committee selected an abstract featuring preclinical data from the Company’s FT538 and FT573 programs for showcase at the SITC (Free SITC Whitepaper) 2021 Annual Meeting Press Conference (Press release, Fate Therapeutics, NOV 9, 2021, View Source [SID1234594878]). The selected abstract entitled "Off-the-shelf, engineered iPSC-derived NK cells mediate potent cytotoxic activity against primary glioblastoma cells and promote durable long-term survival in vivo" will be presented by Jeffrey S. Miller, M.D., Professor of Medicine, University of Minnesota and Deputy Director, Masonic Cancer Center. The press conference is being held on Wednesday, November 10 from 12:30-2 pm ET.

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Dr. Miller’s presentation will describe the anti-tumor activity of the Company’s FT538 clinical product candidate as monotherapy and in combination with an NK cell engager targeting B7-H3, an immune checkpoint transmembrane protein overexpressed on many human cancer cells and commonly associated with poor prognosis. The presentation will also describe the integration of a novel chimeric antigen receptor (CAR) construct targeting B7-H3 into the master induced pluripotent stem cell (iPSC) line of FT538 to create the Company’s preclinical product candidate FT573, a B7-H3-targeted CAR NK cell incorporating multiple anti-tumor modalities.

In a recently published peer-reviewed article in Cell Stem Cell entitled "Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy", FT538 was shown to share metabolic, transcriptional, and functional features with adaptive NK cells, a rare subset of NK cells with memory-like properties that have a genome-wide epigenetic profile and recall response that parallel cytotoxic effector CD8+ T cells. The published data demonstrate that FT538 exhibits significantly enhanced serial killing and functional persistence compared to peripheral blood NK cells. The superior anti-tumor activity of FT538 was attributable to its novel engineered components, including the knockout of CD38 and the expression of IL-15/IL-15R fusion protein, which were shown to improve metabolic fitness, increase resistance to oxidative stress, and induce a protein expression program that enhanced NK cell activation and effector function. The studies in the Cell Stem Cell publication were conducted as part of a collaboration between scientists at Fate Therapeutics and the laboratory of Dr. Miller, and were led by Frank Cichocki, Ph.D., University of Minnesota.

Investor Event Webcast and Conference Call

The Company will host a live audio webcast on Monday, November 15, 2021 at 4:30 p.m. ET to highlight its emerging pipeline of off-the-shelf, multiplexed-engineered, iPSC-derived NK cell programs for the treatment of solid tumors. In order to participate in the conference call, please dial (877) 303-6235 (domestic) or (631) 291-4837 (international) and refer to conference ID 2793475. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

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.

About FT538
FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636). FT538 is also being investigated in a multi-dose Phase 1 clinical trial in combination with one of an array of tumor-targeting monoclonal antibodies for the treatment of advanced solid tumors (NCT05069935).

Celsion Corporation to Hold Third Quarter 2021 Financial Results and Business Update Conference Call on Monday, November 15, 2021

On November 9, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage development company focused on DNA-based immunotherapy and next-generation vaccines, reported that the Company will host a conference call at 11:00 a.m. ET on Monday, November 15, 2021 to discuss financial results for third quarter ended September 30, 2021 and provide an update on product development programs with GEN-1, a DNA-based immunotherapy, currently in Phase II development for the localized treatment of advanced ovarian cancer and PLACCINE, a proprietary synthetic, non-viral vaccine delivery technology currently in preclinical studies. Celsion has two platform technologies for the development of novel nucleic acid-based immunotherapies and next generation infectious vaccines (Press release, Celsion, NOV 9, 2021, View Source [SID1234594877]).

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To participate in the call, interested parties may dial 1-800-353-6461 (Toll-Free/North America) or +1-334-323-0501 (International/Toll) and ask for the Celsion Corporation Third Quarter 2021 Earnings Call (Conference Code: 4154518) to register ten minutes before the call is scheduled to begin. The call will also be broadcast live on the internet at www.celsion.com. The call will be archived for replay on Monday, November 15, 2021 and will remain available until November 29, 2021. The replay can be accessed at +1-719-457-0820 or 1-888-203-1112 using Conference ID: 4154518 . An audio replay of the call will also be available on the Company’s website, www.celsion.com, for 90 days after 2:00 p.m. ET Monday, November 15, 2021.

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).

Seagen to Highlight Two Novel Antibody-Drug Conjugates (ADCs) at the SITC 36th Annual Meeting

On November 9, 2021 Seagen Inc. (Nasdaq:SGEN), reported the presentation of two new vedotin-based antibody-drug conjugate (ADC) programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Anniversary Annual Meeting, taking place in Washington, D.C. and virtually, November 10-14, 2021 (Press release, Seagen, NOV 9, 2021, View Source [SID1234594875]). Each program combines antibodies targeted to an immune checkpoint [PD-(L)1 or B7-H4] with the cytotoxic properties of the vedotin payload. Preclinical data demonstrate promising antitumor activity. Both ADCs are set to enter first-in-human phase 1 studies in 2022.

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"We are excited to advance two novel immune checkpoint vedotin ADCs, SGN-PDL1V and SGN-B7H4V, into phase 1 studies. These programs utilize a clinically validated payload and have the potential to be first in class ADCs," said Roger Dansey, M.D., Chief Medical Officer at Seagen.

SGN-PDL1V is a novel, investigational vedotin ADC directed to the T cell checkpoint ligand, PD-(L)1. PD-(L)1 is a target with limited normal tissue expression and clinically validated expression across a variety of malignancies, including non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinomas (HNSCC). SGN-PDL1V is engineered for efficient delivery of the therapeutic payload, monomethyl auristatin E (MMAE), and is proposed to have distinct mechanisms of action from other PD-(L)1-directed therapeutics, including direct cytotoxicity against PD-(L)1-expressing cells, bystander killing, and immunogenic cell death. SGN-PDL1V demonstrates robust antitumor activity in xenograft models, including in tumors with low, heterogenous PD-(L)1 expression, supporting the potential to treat patients across a wide range of PD-(L)1 expression levels. (Abstract #783)

SGN-B7H4V is a novel, investigational vedotin ADC directed to the T cell checkpoint ligand, B7-H4. B7-H4 expression is limited on normal tissue and overexpressed on a variety of solid malignancies, including breast, ovarian, and endometrial tumors. SGN-B7H4V is designed to bind and internalize the B7-H4/ADC complex from the surface of the tumor cells and release the therapeutic payload MMAE, inducing MMAE-mediated direct cytotoxicity, bystander killing, and immunogenic cell death, as well as antibody-dependent cellular cytoxicity (ADCC) and phagocytosis (ADCP). SGN-B7H4V demonstrates strong activity in xenograft models, including models with heterogenous B7-H4 expression. (Abstract #854)

The abstracts published in advance of the SITC (Free SITC Whitepaper) Annual Meeting can be found here. All data presentations will be available on-demand starting on November 9.