On April 8, 2022 OncoMyx Therapeutics, a privately-held oncolytic virus immunotherapy company, reported the presentation of new preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 being held April 8-13 (Press release, OncoMyx Therapeutics, APR 8, 2022, View Source [SID1234611689]). The data presented at AACR (Free AACR Whitepaper) 2022 demonstrate that OncoMyx’s myxoma virus multi-armed with IL-12 and decorin infects and kills human multiple myeloma cells in vitro and demonstrates dose responsive efficacy after intravenous (IV) administration in a mouse model of multiple myeloma.

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"These data demonstrate that OncoMyx’s multi-armed myxoma virus works via direct oncolytic activity as well as immunomodulation of both the innate and adaptive immune response, including T cells and natural killer (NK) cells," said Leslie L. Sharp, Ph.D., chief scientific officer of OncoMyx. "As we look toward the clinic, we have generated a substantial amount of data on the safety and efficacy of our multi-armed myxoma virus and look forward to moving into GMP manufacturing and IND-enabling activities."

"OncoMyx’s myxoma virus is the first large, multi-armed oncolytic virus to demonstrate efficacy in preclinical models of multiple myeloma," said Steve Potts, Ph.D., MBA, cofounder and CEO of OncoMyx. "We continue to demonstrate the differentiated efficacy and immunomodulatory properties of OncoMyx’s multi-armed myxoma virus and its potential to be effective across a broad range of cancers, from hematological malignancies to solid tumors."

Substantial published research demonstrates that the myxoma virus naturally and selectively replicates in human tumor cells, infects and kills multiple myeloma cells, and stimulates the immune system. Furthermore, the large size of the myxoma genome allows for the insertion of multiple genes to arm the virus with immune modulators that can orchestrate the cancer-immunity cycle for optimal viral-mediated cancer-killing activity. OncoMyx has multi-armed myxoma virus to carry IL-12, an immune modulator, and decorin, which can affect tumor cell intrinsic signaling and microenvironment modulation.

The poster (abstract #5618) titled, "Multi-armed myxoma virus has therapeutic potential for treatment of multiple myeloma," will be available on the AACR (Free AACR Whitepaper) Annual Meeting 2022 website for registered attendees to view from Friday, April 8 through Wednesday, July 13. The poster will also be available on OncoMyx’s website.

​​About OncoMyx’s Myxoma Immunotherapy Platform

OncoMyx’s multi-armed myxoma virus delivers multiple antitumor immunomodulatory proteins that target critical points in the cancer immunity cycle to modulate the tumor microenvironment and stimulate a robust anti-tumor response. Myxoma is a natural oncolytic virus, selectively infecting and killing a wide range of cancer cell types. It is also inherently highly immuno-interactive, and as a large dsDNA poxvirus, can be engineered to express multiple payloads to treat cancer. Because myxoma is not pathogenic to humans, there is no pre-existing immunity, making it highly amenable to intravenous and repeat dosing.

On April 8, 2022 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 the presentation of interim data from a first-in-human, Phase 1 study evaluating PRTX007, 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 New Orleans (Press release, Primmune Therapeutics, APR 8, 2022, View Source [SID1234611687]). The study is a 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 is administered orally to adult healthy volunteers. In addition to assessing the safety, tolerability and pharmacokinetics of PRTX007, the study is designed to evaluate pharmacodynamic responses relevant to dose selection for patients with cancer.

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"These data from our ongoing first-in-human trial indicate that Primmune’s lead candidate, PRTX007, is well-tolerated in healthy volunteers and activates the desired components of innate and downstream adaptive immune responses while avoiding induction of proinflammatory cytokines," said James Appleman, Ph.D., Co-Founder and Chief Scientific Officer at Primmune Therapeutics. "We look forward to the clinical advancement of PRTX007 for the treatment of solid tumors in combination with checkpoint inhibitors and as a monotherapy for the treatment of human papillomavirus-driven pre-cancerous cervical lesions and the underlying infection."

Data show that PRTX007 was well-tolerated and expressed a favorable safety profile in the analyzed patient cohorts, with most adverse events (AEs) considered incidental and no instances of moderate, severe or serious AEs. In addition, every other day (QOD) dosing demonstrated stable systemic immune induction without evidence of counter-regulation. Both the clinical characteristics and unique pattern of immune induction by PRTX007 support its use in combination with immune checkpoint inhibitors.

Presentation Title: PRTX007, an Optimized TLR7 Agonist for Systemic Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)s: Interim Analysis of Phase I Study in Healthy Volunteers Presenting Author: Curtis Scribner, M.D., Chief Medical
Presenting Author: Curtis Scribner, M.D., Chief Medical Officer, Primmune
Abstract Number: 1865
Poster Number: CT189
Poster Board Number: 14
Poster Session: Phase I Clinical Trials 2 Session
Session Date and Time: Tuesday, April 12, 9 a.m. to 12:30 p.m. CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 33

Additional highlights from the poster presentation include:

Most AEs were incidental and not dose related. The most common drug-related AE was headache, seen across both treated and placebo groups independent of dose.
At the interim analysis, PRTX007 demonstrated a favorable safety profile when administered orally to all 9 SAD and 3 MAD cohorts tested.
PRTX007 demonstrated induction of interferon-stimulated genes (ISGs) without significant increases in circulating interferons (IFNs). There was no increase in expression or circulating levels of proinflammatory cytokines (e.g., TNFα, IL-6, IL-1β)
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 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. Furthermore, activated pDCs directly deliver interferons to target cells by paracrine transfer. This is functionally equivalent to administering a cocktail of all Type I/III IFN while avoiding the associated side effects and adverse events. PRTX007 is being rapidly advanced towards clinical trials for solid tumors in the advanced cancer setting and for clearing human papillomavirus-driven pre-cancerous cervical lesions.

On April 8, 2022 Nykode Therapeutics AS (Euronext Growth (Oslo): NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of vaccines and novel immunotherapies, reported preclinical data from its second-generation Vaccibody Antigen-Presenting Cell (APC)-targeting vaccine technology, which incorporates immune-stimulatory cytokines (Press release, Nykode Therapeutics, APR 8, 2022, View Source [SID1234611686]). The data will be presented in a poster session at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on Tuesday, April 12, 2022, from 1:30 p.m. – 5:00 p.m. ET.

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"The preclinical data reported at AACR (Free AACR Whitepaper) highlights that Nykode’s unique vaccines co-expressed with immune-stimulatory proteins can produce a nearly three-fold boost in anti-tumor immune cell response in comparison to the first-generation platform. The research showcases the advantages of Nykode’s APC-targeted delivery of tumor specific antigens and its ability to successfully induce a powerful immune response against tumor cells, overcoming a historical challenge in the development of cancer vaccines. We look forward to continued innovation in our platform as we advance our pipeline of vaccine candidates through the clinic," said Mikkel Pedersen, Chief Scientific Officer of Nykode Therapeutics.

The preclinical results demonstrate that the co-expression of the Vaccibody molecule and immune-stimulatory cytokines enhances anti-tumor immune responses, leads to an expansion of antigen-specific polyfunctional effector T cells and superior tumor control. In addition, the data demonstrate that the second-generation platform enhances APC infiltration, proliferation and differentiation, measured by live CD45+ infiltrated cells and the proportion of DCs in live CD45+ cells, including cDC1.

Details of the poster presentation are as follows:

Abstract #: 2232
Title: A novel and versatile cytokine empowered DNA vaccine platform with superior immune activating potential
Authors: Beraas, et al.
Session Title: Vaccines: Oncolytic and Prophylactic
Session Date and Time: Tuesday, April 12, 2022 | 1:30 p.m. – 5:00 p.m. ET

The poster presentation is available in the AACR (Free AACR Whitepaper) 2022 Annual Meeting program and in the Scientific Papers and Presentations section of the Company’s website.

On April 8, 2022 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported the presentation of new data from its preclinical-stage IL-18 and LAG3-targeted IL-15 cytokine programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Xencor, APR 8, 2022, View Source [SID1234611684]).

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"XmAb cytokines are engineered to be long acting and more drug-like in order to overcome inherent limitations facing cytokine therapeutics. At AACR (Free AACR Whitepaper), we are presenting two additions to our wholly owned cytokine portfolio — a decoy-resistant and potency-reduced IL18-Fc fusion protein, and a LAG-3 targeted IL15/IL15Rα-Fc fusion protein, which is biased toward binding and activating LAG-3-positive lymphocytes that are more likely to be tumor-reactive," said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. "Later this year we plan to submit an investigational new drug application for XmAb662, our wholly owned, reduced-potency IL12-Fc cytokine, which has demonstrated remarkable preclinical anti-tumor activity and improved therapeutic index in vivo."

The posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

Abstract 2080, "LAG3-targeted IL15/IL15Rα-Fc (LAG3 x IL15) fusion proteins for preferential TIL expansion"

Session: Immunomodulatory Agents and Interventions 1
Date and Time: Monday, April 11, 2022, 1:30 – 5:00 p.m. CDT
Location: Exhibit Halls D-H, Section 38, Board 18
IL-2 and IL-15 are cytokines that cause the activation and proliferation of T cells and NK cells. Their therapeutic potential has been well established in preclinical models and clinical studies; however, when given systemically, these potent cytokines have historically provided a poor therapeutic window, as they are not well tolerated and are quickly cleared from circulation.

Xencor engineered LAG3-targeted IL15/IL15Rα-Fc cytokine/antibody fusion proteins (LAG-3 x IL-15) for selective activation of LAG3-positive immune cells, which may potentially avoid systemic toxicities arising from off-target activation and expansion of peripheral immune cells. An XmAb heterodimeric Fc domain serves as a molecular scaffold, and Xtend technology promotes longer circulating half-life. LAG-3 is an immune checkpoint expressed on tumor-infiltrating lymphocytes (TILs), is frequently co-expressed with PD-1 and has limited expression in normal peripheral immune cells. Recently, anti-LAG3 agents have generated promising results in clinical studies, and LAG-3 x IL-15 agents could be combined with anti-PD1 agents. Xencor’s LAG-3 x IL-15 candidate molecules demonstrated high selectivity for LAG3-positive cell populations in multiple in vitro and in vivo models.

Abstract 3515, "Engineered IL18 heterodimeric Fc-fusions featuring improved stability, reduced potency, and insensitivity to IL18BP"

Session: Immunomodulatory Agents and Interventions 2
Date and Time: Tuesday, April 12, 2022, 1:30 – 5:00 p.m. CDT
Location: Exhibit Halls D-H, Section 37, Board 17
IL-18 is a proinflammatory cytokine that modulates both the innate and adaptive immune responses. IL-18 receptor 1, the primary co-receptor for IL-18, is overexpressed on activated T cells and NK cells, which are critical for anti-tumor responses. Additional preclinical studies of IL-18 have demonstrated its anti-tumor activity, including synergy with immune checkpoint inhibitors and CAR-T therapies. In contrast with other potent cytokines, IL-18 has been well tolerated in clinical trials but demonstrated a lack of efficacy despite heavy dosing. IL-18 participates in a negative feedback loop with a high affinity natural inhibitor, IL18BP, which was observed to be upregulated in early phase clinical studies and may have directly resulted in IL-18’s limited clinical performance.

Xencor engineered stabilized, potency-reduced, monovalent IL-18 cytokines fused to an XmAb heterodimeric Fc domain with Xtend Fc technology for longer half-life. Importantly, these cytokine-Fc fusions were engineered to not bind its inhibitor, IL18BP. In a preclinical mouse model of graft-versus-host disease, an analog of the candidate XmAb143 led to the expansion and proliferation of target immune cells and induced high levels of interferon gamma. Further, it was well tolerated in non-human primates and exhibited favorable pharmacokinetics, such as slow receptor-mediated clearance.

On April 8, 2022 Nimbus Therapeutics, a clinical-stage company reported that designs and develops breakthrough medicines through its powerful computational drug discovery engine, is sharing preclinical data, on its Casitas B-lineage lymphoma b (Cbl-b) inhibitor, NTX-801, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, being held April 8-13, 2022, in New Orleans, LA (Press release, Nimbus Therapeutics, APR 8, 2022, View Source [SID1234611683]).

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Cbl-b is an E3 ubiquitin ligase that is expressed in immune cells and, in the context of cancer, acts as a brake on the immune system, functioning as an intracellular checkpoint that negatively regulates T-cell activation, natural killer cell activity and immune response through degradation of specific proteins. Taken together, these factors make Cbl-b inhibition a potentially promising target for immuno-oncology.

Nimbus employed a structure-based drug design approach to identify small molecule inhibitors of Cbl-b. The inhibitor NTX-801 demonstrated strong immune cell activation and robust and statistically significant tumor growth inhibition in a mouse syngeneic tumor model. In combination with anti-PD-1, it resulted in robust anti-tumor activity, increased survival, and several complete responses, as defined by no measurable tumor in the murine tumor model.

"Preventing Cbl-b activity from dampening immune responses has long been seen as a promising potential way to enhance anti-tumor immunity. The preclinical data we are presenting today at AACR (Free AACR Whitepaper) support the promise of Cbl-b inhibition as a means of activating the immune response in vivo," said Peter J. Tummino, Chief Scientific Officer. "We look forward to further characterizing the Cbl-b inhibitors we have identified, and continuing to advance Cbl-b inhibition toward the clinic as a novel immuno-oncology approach."

The details of the poster presentation are as follows:

Title: Discovery of NTX-801, a Cbl-b inhibitor with antitumor activity in syngeneic models
Session Category: Immunology
Session Title: Immune Checkpoints
Session Date and Time: Sunday, April 10, 2022, 1:30 PM – 5:00 PM ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 38
Poster Number: 28