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

On April 8, 2022 Theratechnologies Inc. ("Theratechnologies" or "the Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported the Company’s participation in three poster presentations at the 2022 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) to be held April 8-13, 2022 at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, Theratechnologies, APR 8, 2022, View Source [SID1234611681]).

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Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer, Theratechnologies commented, "The exciting new data in triple negative breast and ovarian cancer demonstrate remarkable promise of TH1902 in preclinical studies as a potential treatment for these sortilin expressing cancers. The presence of cancer stem cells (CSCs) is associated with aggressive disease, unregulated tumor growth, increased migration of cancer cells, invasion, self renewal and resistance to standard chemotherapy and radiation. Failure to eliminate these cells with current treatments leads to resistance and progression and there are few therapies that have been shown to target CSCs. In preclinical models treated with TH1902, there was marked tumor growth inhibition of cancer stem-like cells with no impact on healthy tissue. This further validates our hypothesis that TH1902 may be effective in hard-to-treat, resistant cancers."

Highlights of the poster presentations included:

AACR Poster #1853 – TH1902, a SORT1 docetaxel peptide-drug conjugate, inhibits tumor growth of human cancer stem-like cells (CD133+) from both triple-negative breast cancers and ovarian cancers

Cancer stem cells, typically associated with CD133 expression, represent a small proportion of cells residing within most tumors and which have high metastatic potential and enhanced drug resistance. In cancer indications such as triple negative breast and ovarian cancers, CSC have also been shown to be involved in vasculogenic mimicry. The study examined the efficacy of TH1902 against cancer stem-like cells and its ability to circumvent some of the known drug resistance phenotypes associated with CSCs. Results included:

The proprietary peptide TH19P01 – Uptake of TH19P01 was exhibited in both cancer stem-like cell lines, but was inhibited by either sortilin ligands or gene silencing, suggesting that the peptide is highly targeted to sortilin expression which is absent in healthy cells.

In vitro – TH1902 induced a marked increase in cell apoptosis – In contrast to docetaxel alone, not only did TH1902 induce cell apoptosis but also produced cell cycle arrest but did not affect healthy tissue.

In vitro — TH1902 bypasses the P-gp efflux pump – Where P-gp inhibitors can restore cell cycle arrest induced by docetaxel, TH1902 was unaffected.

In vivo — triple negative breast and ovarian cancer models – TH1902 significantly inhibited growth of cancer stem-like cell tumor when administered weekly for 3 cycles at a dose equivalent to the MTD of docetaxel and TH1902 treated mice exhibited an increased tolerability when compared to those treated with docetaxel alone.

TH1902 demonstrated better efficacy at doses equivalent to docetaxel – As a single agent in breast and ovarian cancer stem-like cell xenograft tumor models, TH1902 showed better efficacy as compared to docetaxel alone. Better efficacy was also observed in the ovarian tumor model for the TH1902-carboplatin combination as compared to paclitaxel- or docetaxel-carboplatin combinations.

An 80% decrease in tumor growth was observed in TH1902 treated models while tumor volumes diminished about 35% in docetaxel mouse models – The results demonstrated that TH1902 exerts superior anticancer activity as compared to docetaxel alone in CD133+ triple negative breast and ovarian cancer stem-like cell animal models.

AACR Poster #1076 – The peptide-drug conjugate TH1902 inhibits growth of subcutaneous melanoma xenografts and formation of lung metastases in a syngeneic mouse model

Highlights of the study demonstrated Theratechnologies’ proprietary peptide-drug conjugate, TH1902, demonstrated better and sustained efficacy in melanoma subcutaneous xenograft models at doses equivalent to the MTD of docetaxel. Mice treated with TH1902 showed prolonged survival by up to 263%, whereas docetaxel alone increased survival by only 19%.

In a lung B16-F10 metastasis model, different regimens of TH1902 significantly reduced the number of lung metastatic nodules when compared to docetaxel alone.

AACR Poster #1079 – Anti-cancer efficacy of TH1902, a SORT1 docetaxel peptide-drug conjugate, against ovarian and endometrial cancers xenografts alone or in combination with carboplatin

Highlights of the poster detailed efficacy of TH1902 against SORT1+ ovarian (ES-2, SKOV-3. A-2780) and endometrial (AN3-CA) tumor models. In vitro, TH1902 enabled a more than twofold increase in apoptosis (cell death) as compared to docetaxel alone. In vivo xenograft tumor models, mice treated with TH1902 over two weeks exhibited a statistically significant 78% decrease in tumor size. Highlights demonstrated TH1902 treated mice showed prolonged tumor regression as compared to mice treated with docetaxel alone.

Mice treated with TH1902 in combination with carboplatin demonstrated better efficacy than other combinations. Results indicated that TH1902 possesses an in-vivo efficacy superior to that of docetaxel against ovarian and endometrial cancers in the animals tested and that TH1902 can be safely combined with carboplatin to reach optimal inhibition of tumor growth.

All three posters will be available on our website following the conclusion of the meeting.

On April 8, 2022 Biomea Fusion, Inc. (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, reported new data at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating BMF-219’s potent and highly effective activity in multiple preclinical models of DLBCL, MM, and KRAS human ex vivo tumor models and cell lines in poster presentations (Press release, Biomea Fusion, APR 8, 2022, View Source [SID1234611679]). In addition, the company presented a Trial In Progress (TIP) poster presentation detailing the design of Biomea’s ongoing Phase I clinical trial (COVALENT-101).

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The preclinical and TIP presentations can be viewed on Biomea’s website at View Source

"Today, we unveiled a dataset in which single agent BMF-219 demonstrated pronounced cytotoxic activity across multiple liquid and solid tumor types that we will be pursuing in the clinic. These data clearly show BMF-219’s powerful cell-killing activity in a broad spectrum of tumor types, including a very robust pan-KRAS effect," said Steve Morris, MD, Biomea’s Chief Medical Officer. "In liquid and solid tumor preclinical studies, BMF-219 has demonstrated a highly differentiated profile from both non-covalent menin inhibitors as well as clinical-stage and FDA-approved covalent KRAS G12C inhibitors. We are very excited to see how this differentiated profile translates in the clinical setting across multiple liquid and solid tumors."

In comparison to two highly specific KRAS G12C inhibitors, BMF-219 exhibited broader potency across KRAS-mutated cell lines (G12C, G12D, G13D, and G12V) and ex vivo PDX tumor models indicating pan-KRAS activity with over 90% growth inhibition in most of these models. Additionally, BMF-219 showed the potential to increase the depth of response across G12C cell lines, notably achieving a higher percentage of cell killing in G12C colorectal cancer cells compared to the commercially available KRAS inhibitor sotorasib and another clinical-stage KRAS inhibitor. Additionally, BMF-219 exhibited robust growth inhibition as a single agent against high-grade B-cell lymphoma cell lines that are known to have low response to standard of care, as well as in multiple MM cells with TP53 and RAS mutations at similar drug concentrations.

A targeted pan-KRAS inhibitor has the potential to treat the 25-35% of NSCLC, 40-45% of CRC, and ~90% of pancreatic cancer patients who have KRAS-mutant tumors. If approved, BMF-219 could be an effective treatment for relapsed/refractory DLBCL and MM, where patients have a significant unmet need despite a large armamentarium of therapeutic options. Additionally, we believe BMF-219 has the potential to be an effective therapeutic option for menin-dependent acute leukemias, including the >45% of AML patients that are believed to have menin-dependent disease.

Poster Presentation Details

Details for the upcoming presentations are as follows:

Anti-tumor activity of irreversible menin inhibitor, BMF-219, in high-grade B-cell lymphoma and multiple myeloma preclinical models (Abstract #1205)

Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Targets and Pathways
Session Date and Time: Tuesday, April 12, 2022 9:00 AM – 12:30 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 24
Poster Board Number: 23
Permanent Abstract Number: 2654

Irreversible menin inhibitor, BMF-219, inhibits the growth of KRAS-mutated solid tumors (Abstract #1202)

Session Category: Experimental and Molecular Therapeutics
Session Title: Signaling Pathway Inhibitors
Session Date and Time: Tuesday, April 12, 2022 9:00 AM – 12:30 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 25
Poster Board Number: 8
Permanent Abstract Number: 2665

COVALENT-101: ​A Phase 1 study of BMF-219, a novel oral irreversible menin inhibitor, as a single agent in patients with relapsed/refractory (R/R) acute lymphocytic/acute myeloid leukemia (ALL/AML), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM) (NCT05153330)​ (Abstract #7613)

Session Category: Clinical Trials
Session Title: Phase I Trials in Progress 1
Session Date and Time: Tuesday, April 12, 2022 9:00 AM – 12:30 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 34
Poster Board Number: 10
Permanent Abstract Number: CT210