On April 18, 2023 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the presentation of new preclinical data for SRF114, a fully human anti-CCR8 antibody, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, Florida (Press release, Surface Oncology, APR 18, 2023, View Source [SID1234630261]). The data will be presented in a poster session (abstract #5125) being held today.

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"We are highly encouraged by these new preclinical data which indicate that therapeutic depletion of CCR8 positive tumor infiltrating Tregs results in robust anti-tumorigenic activity in both checkpoint inhibition-resistant and checkpoint inhibition-susceptible tumor models," said Vito Palombella, PhD, chief scientific officer, Surface Oncology. "These data bolster our belief that SRF114 holds the potential to become a best-in-class anti-CCR8 treatment and further support our ongoing Phase 1 clinical investigation of SRF114 in patients with advanced solid tumors."

Summary of key data

In human CCR8 knock-in mice, SRF114, a fully human antibody targeting human CCR8, conferred robust anti-tumor activity and reshaped the tumor microenvironment towards a proinflammatory milieu.
In different in vivo models, SRF114 monotherapy or treatment with a murine surrogate antibody promoted expansion of CD8+ effector T cells and increased the production of pro-inflammatory molecules including IFNγ, TNFα, and granzyme A in a checkpoint-resistant tumor model.
Anti-CCR8 therapy resulted in depletion of tumor Tregs without impacting peripheral lymphoid Treg cell populations and led to increases in the levels of co-stimulatory molecules CD80 and CD86 in a subset of tumor myeloid cells.
Anti-CCR8 and anti-PD-1 combination therapy increased tumor immune cell infiltration, cytokine production and improved overall survival in a checkpoint inhibitor resistant melanoma model.
Poster Session Information
Title: Depletion of CCR8+ tumor Treg cells with SRF114 or anti-CCR8 therapy promotes robust antitumor activity and reshapes the tumor microenvironment toward a more pro-inflammatory milieu
Abstract number: 5125
Session category: Immunology
Session title: Combination Immunotherapies 2
Session date and time: Tuesday, April 18, 2023, from 1:30 p.m. to 5:00 p.m. ET

A copy of the poster will be available on the Posters & Publications page of the company’s website following the presentation.

About SRF114
SRF114 is a fully human, afucosylated anti-CCR8 antibody designed to preferentially deplete CCR8+ Treg cells within the tumor microenvironment. In preclinical studies, Surface Oncology has shown that SRF114 induces antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) pathways to deplete intratumoral Treg cells. In addition, SRF114 reduced tumor growth in murine models. These findings support the advancement of SRF114 as a therapeutic candidate that holds the potential to drive anti-tumor immunity in patients.

On April 18, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported new preclinical data on its SNS-103 program aimed at developing a conditionally active, monoclonal antibody program targeting ENTPDase1 (also known as CD39) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (Press release, Sensei Biotherapeutics, APR 18, 2023, View Source [SID1234630260]).

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"CD39 is an important target because it is the rate-limiting enzyme that creates an immunosuppressive tumor microenvironment through the production of adenosine. However, it has been difficult to target effectively due to its broad expression on various cells in both tumors and normal tissues," said Edward van der Horst, Ph.D., Chief Scientific Officer at Sensei Biotherapeutics. "The hypothesis driving our program is that a pH-sensitive antibody may inhibit the pro-tumoral activities of CD39 selectively within the tumor microenvironment while avoiding on-target/off-tumor binding and pharmacokinetic issues observed with prior CD39 antibodies."

Presentation highlights:

Poster presentation titled, "Identification of conditionally active antibodies that selectively block CD39 activity in the acidic tumor microenvironment"

CD39 is commonly upregulated in the tumor microenvironment, which is characterized by high levels of extracellular ATP (eATP) and low pH. Upregulation and activation of CD39 results in significant reductions of eATP and a rise in immunosuppressive adenosine.
SNS-103 is aimed at developing an antibody that binds to CD39 only under low pH conditions such as those found in the tumor microenvironment and achieves a high target occupancy selectively in the tumor, while maintaining extracellular ATP and inhibiting adenosine generation to enhance anti-tumor immunity.
From a panel of 83 antibodies identified and characterized for CD39 inhibition at neutral and acidic pH, Sensei has selected 8 antibodies for further optimization.
Sensei intends to select a lead product candidate for SNS-103 in 2023.
The full poster is available for viewing on Sensei’s corporate website.

On April 18, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported a positive review of the ongoing Phase 3 REGAL clinical trial of galinpepimut-S (GPS) in acute myeloid leukemia (AML) (Press release, Sellas Life Sciences, APR 18, 2023, View Source [SID1234630259]). The Independent Data Monitoring Committee (IDMC) performed a routine, prespecified risk-benefit assessment of unblinded data from the study and has recommended that the trial continue without modifications. The IDMC has further recommended to meet again within Q3 2023 and endorsed all clinical trial initiatives SELLAS has undertaken to advance GPS in the REGAL study, including the addition of clinical sites in China.

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"This positive IDMC review marks another significant milestone in GPS development and builds on the favorable profile of our study drug, galinpepimut-S," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "Enrollment continues in our global Phase 3 REGAL registrational study, which currently remains on track for interim analysis by the end of 2023 or early 2024."

REGAL is a Phase 3 open-label registrational clinical trial for GPS in AML patients who have achieved complete remission following second-line salvage therapy (CR2 patients). The primary endpoint is overall survival. The IDMC is an independent group of medical, scientific and biostatistics experts who are responsible for reviewing and evaluating patient safety and efficacy data for REGAL, and for monitoring quality and overall conduct to ensure the validity, scientific and clinical merits of the study. The IDMC charter provides for periodic reviews for safety, efficacy, and futility in addition to the interim and final analyses.

On April 18, 2023 QIAGEN N.V. (NYSE: QGEN) (Frankfurt Stock Exchange: QIA) reported its plans to release results for the first quarter 2023 (Press release, Qiagen, APR 18, 2023, View Source [SID1234630258]).

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Press release date / time: Wednesday, May 3, shortly after 22:05 Frankfurt time / 21:05London time / 16:05 New York time.

Conference call date / time: Thursday, May 4, at 15:00 Frankfurt time / 14:00 London time / 09:00 New York time.

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On April 18, 2023 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat solid tumors in the advanced cancer setting and for the clearance of human papillomavirus and related pre-cancerous cervical lesions, reported new clinical data from a first-in-human, Phase 1 study evaluating PRTX007, an orally administered prodrug of a novel, small molecule toll-like receptor 7 (TLR7)-specific agonist, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando, Florida (Press release, Primmune Therapeutics, APR 18, 2023, View Source [SID1234630257]).

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The study was a first-in-human, Phase 1, single-center, prospective, randomized, double-blind, placebo-controlled study with 9 single-ascending dose (SAD) cohorts and 4 multiple-ascending dose (MAD) cohorts where PRTX007 was administered orally to adult HVs. In addition to assessing the clinical safety and tolerability of PRTX007, the study was designed to evaluate the pharmacokinetics of PRTX007 and identify the specific active dosing range for use in future cancer studies.

Consistent with interim results from the Phase 1 study, data show that PRTX007 was well-tolerated and expressed a favorable safety profile in all of the analyzed cohorts, with no serious adverse events (AEs) or AEs at or above grade 3. Every other day (QOD) dosing in the 750mg cohort demonstrated stable systemic induction of the innate and adaptive immune responses, with significant increases in CD8+ T cells and NK cell activation (CD38+ markers) observed from pretreatment to end of dosing in all HVs. There were no systemic increases in proinflammatory factors observed for any dose range in the Phase 1 study. Both the clinical characteristics and unique pattern of immune induction by PRTX007 support its use in combination with immune checkpoint inhibitors.

"These Phase 1 results set the stage for PRTX007 to enable long-term continuous immune induction in combination with other therapeutic modalities including checkpoint inhibitors and as a single agent," said James Appleman, Ph.D., Co-Founder and Chief Scientific Officer at Primmune Therapeutics. "PRTX007 was shown to activate innate and downstream adaptive immune responses without significant increases in circulating proinflammatory cytokines, demonstrating its potential to deliver the therapeutic benefit that patients need while avoiding dose-limiting adverse events. The Primmune team is encouraged by our positive Phase 1 data and we look forward to the ongoing clinical development of PRTX007."

Presentation details:

Title: Activation of Innate and Adaptive Immune Response with a Clinical Stage TLR7 Agonist Prodrug PRTX007
Presenting Author: Curtis Scribner, M.D., Chief Medical Officer, Primmune
Abstract Number: CT180
Poster Board: 12
Session Title: First-in-Human Phase I Clinical Trials 2
Session Date and Time: Tuesday, April 18, 9:00 a.m. ET to 12:30 p.m. ET
Location: Orange County Convention Center, Poster Section 45

Additional highlights from the poster presentation include:

PRTX007 demonstrated a favorable safety profile when administered orally to all 9 SAD and 4 MAD cohorts tested.
Most AEs were mild and not dose-related, with no instances of dose modification or discontinuation due to treatment-related AEs throughout the study. The most common drug-related AE was headache, seen across both treated and placebo groups independent of dose.
PRTX007 demonstrated well-controlled expression of interferon-stimulated genes (ISGs) independent of dose, without significant increases in circulating IFNs. There was no increase in expression or circulating levels of proinflammatory cytokines (e.g., TNFα, IL-6, IL-1β).
CD8+ T cells and NK cell activation (CD38+ markers) increased markedly from pretreatment to end of dosing in all HVs.
These data justify further exploration of PRTX007 as a potential cancer therapeutic. Primmune plans to conduct a future study evaluating PRTX007 in combination with a checkpoint inhibitor across the active doses identified in the Phase 1 study for the potential treatment of solid tumors.

About PRTX007
PRTX007, Primmune’s lead clinical development candidate, is designed to provide well-tolerated, controlled, long-term stimulation of the innate immune response while also potentiating long-term effective innate and adaptive immune responses. PRTX007 administration uniquely activates plasmacytoid dendritic cells (pDCs), leading to a systemic immune poly-IFN response without stimulating production of NF-κB-driven proinflammatory factors like IL-6, TNFα or IL-1β. Activated pDCs directly deliver interferons to target cells by paracrine transfer. Conceptually, this is equivalent to administering a therapeutically effective cocktail of all Type I/III IFNs while avoiding the associated side effects and adverse events. Furthermore, PRTX007 administration leads to systemic activation of anti-tumor effector CD8+ T cells and NK cells. PRTX007 is being rapidly advanced towards clinical trials for solid tumors in the advanced cancer setting and for clearing human papillomavirus-transformed pre-cancerous cervical lesions.