On November 10, 2022 Pulmatrix (NASDAQ: PULM), a clinical-stage biopharmaceutical company developing innovative inhaled therapies to address serious disease using its patented iSPERSE technology, reported third quarter financial results for 2022 and provided a corporate update related to its development programs (Press release, Pulmatrix, NOV 10, 2022, View Source [SID1234623685]).

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Ted Raad, Chief Executive Officer of Pulmatrix commented, "In this quarter we have advanced both PUR3100 and PUR1900 towards important data catalysts. We completed patient dosing for PUR3100, our orally inhaled dihydroergotamine (DHE) being developed for the treatment of acute migraine, in a Phase 1 study with data expected to be released in early Q1 2023. In addition to safety and tolerability, the study will evaluate the pharmacokinetics of PUR3100 compared to intravenous DHE. This will allow us to better understand the potential efficacy and tolerability profile of PUR3100, which we believe could be beneficial to patients suffering from acute migraine. We also commenced study start-up activities for the PUR1900 Phase 2 study and remain on track to initiate patient dosing in the first quarter of 2023. PUR1900 has the potential to be the first approved therapy for the treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in patients with asthma."

Third Quarter 2022 and Recent Program Highlights

PUR1900 in development for ABPA

Pulmatrix initiated study start-up activities for the Phase 2 safety and efficacy study of PUR1900 in patients with asthma and ABPA. This will include a 16-week dosing regimen and endpoints that would potentially support a Phase 3 trial.
PUR3100 in development for acute migraine

On September 26, 2022, Pulmatrix announced completion of patient dosing in its Phase 1 trial evaluating PUR3100.
Phase 1 study database lock to occur in November with top-line data anticipated to be released in early Q1 2023.
PUR1800 in development for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)

Pulmatrix is analyzing data from the completed Phase 1b clinical study of PUR1800 for AECOPD for presentation at a relevant medical conference in 2023. These data will inform the design of a potential Phase 2 study in the treatment of AECOPD.
Third Quarter 2022 Financial Results

Revenues increased $0.8 million to $1.9 million for the three months ended September 30, 2022 compared to $1.1 million for the same period in 2021. The increase in revenue was due to $1.9 million in revenue in the three months ended September 30, 2022 for the PUR1900 program related to the Cipla Agreement compared to no revenues for the three months ended September 30, 2021. This was partially offset by no revenues in the three months ended September 30, 2022 for the PUR1800 program compared to $1.1 million for the three months ended September 30, 2021.

For the three months ended September 30, 2022, research and development expenses increased $1.3 million to $5.3 million compared to $4.0 million for the same period in 2021. The increase was primarily due to increased spending of $1.5 million in clinical costs related to the PUR1900 program, $0.6 million in employment costs and $0.2 million in facility costs. This amount was partially offset by a $1.0 million decrease in non-clinical and clinical costs related to the PUR1800 program.

General and administrative expenses were unchanged at $1.7 million for the three months ended September 30, 2022 compared to the same period in 2021.

During the three months ended September 30, 2022, the Company sold 252,013 shares of its common stock at a weighted-average price of approximately $5.70 per share, for net proceeds of approximately $1.4 million, under the At-The-Market Sales Agreement established with H.C. Wainwright & Co., LLC in May 2021.

Cash and cash equivalents as of September 30, 2022 was $40.7 million. As of November 10, 2022, Pulmatrix expects its existing cash and cash equivalents will enable it to fund operating expenses and capital expenditure into the second quarter of 2024.

On November 10, 2022 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 preclinical data will be presented on TALEN-edited smart CAR T-cells overcoming key challenges of targeting solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting (Press release, Cellectis, NOV 10, 2022, View Source [SID1234623684]).

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The data will be presented today in two poster sessions titled: "Multi-armored allogeneic MUC-1 CAR T-cells efficiently control triple negative breast cancer tumor growth" (Poster Number: 217) and "TALEN-edited smart CAR T-cells leverage solid tumor microenvironment for specific and effective immunotherapy" (Poster Number: 325).

The poster presentations highlight the following preclinical data:

Multi-armored allogeneic MUC-1 CAR T-cells efficiently control triple negative breast cancer tumor growth

· This poster highlights TALEN-edited smart CAR T-cells targeting MUC1- expressing solid tumors.

· MUC1 is a tumor-associated antigen that is overexpressed in triple-negative breast cancer (TNBC) and other solid tumor malignancies.

· MUC-1 CAR T-cells infiltrate tumors more efficiently and extend survival when enhanced with attributes catered towards the tumor microenvironment (TME) of TNBC tumors.

· TGFBR2 knock-out (KO) circumvents the inhibitory effects of TGFβ1, and IL-12 release follows CAR T-cell activation pattern restricting it to the tumor site for increased safety.

· Enhanced MUC-1 CAR T-cells could address some of the current challenges in development of CAR Ts for TNBC patients with unmet medical needs.

· Overall, we can efficiently generate allogeneic CAR T-cells and engineer them to overcome several key challenges of immune suppressive solid tumors.

TALEN-edited smart CAR T-cells leverage solid tumor microenvironment for specific and effective immunotherapy

· This poster highlights innovative T-cell engineering strategies designed to increase the activity of CAR T-cells for solid tumors while mitigating toxicity risk.

· Therapeutic efficacy of CAR T-cell therapy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy. Our TALEN-based gene editing platform allows innovative T cell engineering strategies that can combat some of the challenges posed by CAR T cell development for solid tumors.

· Inducible expression of a tumor-antigen directed CAR by a constitutive CAR specific to TME cues greatly enhanced anti-tumor activity, while limiting ‘on target, off-tumor’ cytotoxicity. Additionally, CAR-induced gene expression could boost anti-tumor CART only within the TME.

· Cellectis’ gene editing strategies could increase CAR T cell persistence and anti-tumor activity while staying restricted to the tumor milieu.

· This proof-of-concept study demonstrates the feasibility of developing CART cell engineering strategies that can improve solid tumor targeting while mitigating potential safety risks, paving the way for clinical development.

Laurent Poirot, Ph.D., Senior Vice President Immunology at Cellectis, noted:

"Using our TALEN-based gene editing platform, we have presented innovative T cell engineering strategies that can combat some of the challenges posed by CAR T cell development for solid tumors. We are mitigating potential safety risks, paving the way for clinical development for patients with unmet medical needs."

Presentations will occur today, from 9:00AM until 9:00PM ET, Hall C.

A copy of both poster presentations will be available on Cellectis’ website here, shortly after the event.

On November 10, 2022 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company focused on developing first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, reported the presentation of data on TPST-1120, an oral selective peroxisome-proliferator activated receptor-alpha (PPAR-α) antagonist, and TPST-1495, a dual antagonist of both EP2 and EP4 prostaglandin (PGE2) receptors, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting taking place November 10-12, 2022 in Boston, MA (Press release, Tempest Therapeutics, NOV 10, 2022, View Source [SID1234623683]).

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The biomarker results presented from the TPST-1120 Phase 1 clinical study demonstrate pharmacodynamic changes in circulating blood in patients who received clinical benefit from therapy that are consistent with blocking the activity of PPAR-α. In addition, data presented from TPST-1495 showed that its dual antagonism of EP2 and EP4 generated significantly greater immune activation in human immune cells and anticancer activity in mouse tumor models than single inhibitors of either receptor, or the COX-2 inhibitor, celecoxib.

"As we advance the Tempest pipeline, we continue to generate results that validate and differentiate the novel approaches of our product candidates," said Tom Dubensky, Ph.D., president of Tempest. "For patients who responded to treatment with TPST-1120 in our Phase 1 study, we have identified potential biomarkers in the peripheral blood of immune activation and alleviation of immune suppression. These discoveries may enable us to identify patient populations in future clinical studies that are most likely to benefit from treatment with TPST-1120."

TPST-1120: "Pharmacodynamic and Predictive Biomarkers Associated with Response in Cancer Patients Treated with TPST-1120: a First-in-class, Small Molecule Antagonist of Peroxisome-Proliferator Activated Receptor-Alpha"

In a late-breaking poster presentation, data from a Phase 1 trial with monotherapy and nivolumab combination arms were used to assess gene expression changes in post-treatment whole blood from 30 patients and to perform baseline mutational analysis on ctDNA to identify potential biomarkers. The data showed that seven genes were modulated by TPST-1120 exposure (p<0.05), including genes associated with enhanced immune responsiveness (CXCL16, TNFRSF1A), stimulation of monocytes or macrophages (ITGAX, FCGR2A) and PPAR-α blockade (NCF4). The results were consistent across monotherapy and combination arms. Patients in the combination arm who had a partial response (PR) to treatment had significant elevations (p<0.05) in multiple genes, including those associated with Th17 development (RORC), lipid transport (APOE) and down-regulation of CD155, a TIGIT ligand. Mutational analysis revealed that patients with a PR or stable disease were more likely to bear mutations in isocitrate dehydrogenase (IDH) and phosphatase and tensin homolog (PTEN) compared to patients with progressive disease.

TPST-1495: "Dual Blockade of the EP2 and EP4 PGE2 Receptors with TPST-1495 is an Optimal Approach for Drugging the Prostaglandin Pathway"

In a second presentation, the data demonstrated that TPST-1495 was more effective than EP2 and EP4 single antagonists, and the COX-2 antagonist, celecoxib, in mouse and human whole blood assays. TPST-1495 conferred a near complete restoration of immune function in cellular assays, even in the presence of high PGE2 concentrations. In lung carcinoma tumors and in a spontaneous tumor mouse model of CRC, TPST-1495 decreased tumor size and number of tumors. Immunohistochemistry analysis of the resected small intestine tumors revealed increased immune infiltrate and an enhanced adaptive immune transcriptional profile.

On November 10, 2022 Allakos Inc. (Nasdaq: ALLK), a clinical-stage biotechnology company developing therapeutics which target immunomodulatory receptors present on immune effector cells involved in allergy, inflammatory and proliferative diseases, reported a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37TH Annual Meeting (Press release, Allakos, NOV 10, 2022, View Source [SID1234623682]). The poster presentation highlights pre-clinical data supporting Siglec-10 as a promising myeloid target for enhancing anti-tumor immunity in solid tumors.

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SITC Poster Details:

The poster titled "Antibody blockade of the immunoinhibitory receptor Siglec-10 polarizes tumor-associated myeloid cells and promotes anti-tumor immunity" will be presented on Friday, November 11TH, key findings include:

Siglec-10 is a myeloid inhibitory checkpoint receptor selectively expressed on tumor associated macrophages (TAMs) and dendritic cells (DCs)
Siglec-10 expression is upregulated in multiple solid cancers and inversely correlates with patient survival in colon adenocarcinoma
Siglec-10 antagonist mAb monotherapy treatment inhibited tumor growth in a syngeneic colon adenocarcinoma model in Siglec-10 transgenic mice
Reduced tumor growth was associated with an expansion and activation of TAMs, dendritic cells, and T lymphocytes in the tumor, consistent with the mechanism of action
The poster is both available on the SITC (Free SITC Whitepaper) website (Abstract ID: 1396) as well as the Allakos Scientific Presentations page.

About Siglec-10 and AK007

In proliferative diseases like cancer, blocking immune inhibitory checkpoint receptors can restore the immune system’s ability to identify and kill tumor cells. Therapeutics that target T cell checkpoint receptors, such as PD-1 and CTLA-4, or their ligands, were the first to demonstrate meaningful anti-tumor activity by blocking immune cell inhibition (i.e. removing the brakes).

More recently, ‘don’t eat me’ signals, such as CD47 and CD24, have been identified to be overexpressed in tumors and allow cancer cells to avoid destruction by macrophages and other myeloid cells of the innate immune system. Restoring myeloid cell function has the potential to increase anti-tumor immunity by activating both innate and adaptive immune cells. Strategies which target ‘don’t eat me’ signals or their myeloid checkpoint receptors represent attractive targets for the treatment of cancer.

Siglec-10 is a checkpoint receptor selectively expressed on tumor associated macrophages (TAMs) and dendritic cells (DCs). Siglec-10 functions as an inhibitory receptor through interaction with multiple ligands, including the ‘don’t eat me’ signal CD24 as well as CD52 and VAP-1. Siglec-10 induces immunosuppression and promotes tumor immune escape through interaction with CD24. Similarly, CD52 has been shown to induce inhibition via Siglec-10, indicating that Siglec-10 functions as an inhibitory receptor through multiple ligands. Siglec-10 is elevated in multiple tumor types and increased expression has been inversely correlated with patient survival in multiple solid tumors, suggesting that Siglec-10 may play a role in tumor evasion.

AK007 is a humanized Siglec-10 antagonist antibody designed to block Siglec-10 interaction with all known ligands (CD24, CD52, and VAP-1). By targeting Siglec-10, AK007 has the potential to reverse myeloid suppression and promote anti-tumor immunity by directly blocking the checkpoint receptor irrespective of individual ligand interaction.

Allakos is currently conducting additional pre-clinical studies with AK007.

On November 10, 2022 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported that preclinical data for SNS-101, a conditionally active VISTA-blocking antibody, as well as characterization of VSIG4, an immune checkpoint targeted by Sensei’s discovery-stage SNS-102 program, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting (Press release, Sensei Biotherapeutics, NOV 10, 2022, View Source [SID1234623681]).

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"The data presented at SITC (Free SITC Whitepaper) add to the growing body of evidence that our TMAb platform is a potentially powerful approach for unlocking previously undruggable immune targets. With the advancement of SNS-101, we have a highly pH-selective antibody to VISTA, which is designed to be conditionally active within the tumor microenvironment," said Robert Pierce, M.D., Chief R&D Officer at Sensei. "We have also made exciting progress in our SNS-102 program, with the functional characterization and identification of novel T-cell receptors that may play a role in VSIG4-mediated immunosuppression. We look forward to advancing both programs with an upcoming IND filing for SNS-101 and identification of a lead anti-VSIG4 antibody in 2023."

Presentation Highlights:

Poster presentation titled, "SNS-101, a highly pH-selective VISTA:PSGL-1 inhibitory antibody, potentiates anti-PD-1 sensitivity, expands memory T-cells and enhances tumor infiltration of CD8 T-cells"

Summary: Sensei has developed SNS-101, a conditionally active, human monoclonal IgG1 antibody specific for the protonated, active form of VISTA, which in preclinical studies has demonstrated the ability to disrupt the immunosuppressive VISTA:PSGL-1 interaction, avoid target-mediated drug disposition (TMDD) and mitigate potential cytokine release syndrome (CRS).

SNS-101 did not bind to human or non-human primates (NHP) VISTA+ monocytes, neutrophils and natural killer cells in blood or other normal tissue compartments.
SNS-101 induced significant expansion of naïve CD8 T-cells and memory CD4 and CD8 T-cells in vivo without activation or depletion of monocytes.
SNS-101 exhibited linear elimination kinetics in non-human primates, overcoming TMDD-induced pharmacokinetic limitations observed with other anti-VISTA antibodies.
In an MC-38 syngeneic tumor model, SNS-101 demonstrated significant enhancement of anti-tumor effects in combination with anti-PD-1 antibodies and a dose-dependent increase in CD8+ T-cells.
IND filing for SNS-101 is anticipated in the first half of 2023.
Poster presentation titled, "Functional characterization of the inhibitory activity and identification of novel T-cell receptors for the tumor-associated macrophage receptor VSIG4"

Summary: Sensei characterized endogenous expression patterns of VSIG4 in polarized macrophage populations and showed a robust VSIG4-mediated suppression of primary human T-cells. Additionally, a ligand receptor capture-trifunctional chemoproteomic (LRC-TriCEPS)-based proteomics strategy identified receptors on primary human T-cells that interact with recombinant VSIG4 protein.

Primary monocytes were purified from peripheral blood mononuclear cells and differentiated into macrophages. Multiplexed droplet digital PCR analysis revealed a robust induction of gene expression of VSIG4 following multiple immunosuppressive stimulations.
Development of multiple functional assays demonstrated VSIG4-mediated suppression of primary human CD4 T-cells.
Through the LRC-TriCEPS proteomics screen, a set of potentially novel T cell receptor candidates that interact with VSIG4 were identified.
A Cas9/CRISPR-based target gene knockdown methodology will be implemented for validation of VSIG4-interacting T-cell receptor candidates.
An initial set of pH-selective anti-VSIG4 antibodies have been identified and further optimization is ongoing to identify a lead antibody.
A copy of the presentation materials will be added to the "Events & Presentations" section of the Company’s Investor Relations website at www.senseibio.com.