On April 9, 2021 MiNA Therapeutics, the pioneer in RNA activation (RNAa) therapeutics, reported translational data supporting the favourable immunological effects of MTL-CEBPA and its benefits in combination with other cancer therapies including anti-PD1 checkpoint inhibition (Press release, MiNA Therapeutics, APR 9, 2021, View Source [SID1234577800]). The studies combine pre-clinical research conducted at the Wistar Institute as well as biomarker analysis of the previously completed OUTREACH clinical trial. MTL-CEBPA is the first candidate from MiNA’s pipeline of small activating RNA therapeutics, a new class of medicines to restore normal cell function. The data will be presented during a poster session at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held virtually from April 10 – April 15, 2021.

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"These new translational findings confirm the important role of MTL-CEBPA in cancer immunology," said Robert Habib, CEO of MiNA Therapeutics. "We continue to deepen our understanding of the immunological effects of MTL-CEBPA for the treatment of patients with advanced cancer and other indications and will analyse its effects as part of our ongoing clinical studies. Collectively, the data further demonstrate how RNA activation can access a previously undruggable target for patient benefit."

In pre-clinical studies, MTL-CEBPA was shown to counteract a key cancer immune evasion pathway by inhibiting immune suppression by myeloid cells. MTL-CEBPA was also shown to potentiate the anti-tumour activity of immunotherapies including anti-PD1 in models of lung and colon cancer. In addition, samples were analysed from advanced liver cancer patients treated with MTL-CEBPA as part of the OUTREACH clinical trial. Analysis of mRNA, protein and cellular biomarkers in peripheral blood confirmed that MTL-CEBPA reduced markers associated with immunosuppressive myeloid cells. Analysis of cellular biomarkers in tumour biopsies showed that those patients who responded to MTL-CEBPA combination therapy had high tumour infiltrations of immunosuppressive macrophages prior to treatment, which were depleted with treatment.

The results validate and expand on previously presented pre-clinical research findings on MTL-CEBPA as an immunological combination treatment in liver cancer and colon cancer. MTL-CEBPA demonstrated signals of activity in a Phase 1b trial in advanced liver cancer, including durable and complete tumour responses as a combination treatment with a standard of care tyrosine kinase inhibitor. A Phase 2 study in advanced liver cancer is expected to commence later this year. MTL-CEBPA is currently being evaluated in a second study in patients with advanced solid tumours in the TIMEPOINT Phase 1/1b clinical trial in combination with a leading checkpoint inhibitor.

The poster will be made available on the Company’s website in the Publications section under "RNA Activation" at the start of the conference on April 10th, 2021.

Presentation information

Title: Up-regulation of C/EBPα inhibits suppressive activity of myeloid cells and potentiates antitumor response in mice and cancer patients
Abstract No: 1730
Session: Immunology – Immunomodulatory Agents and Interventions
Presenter: Mikael Sodergren

About MTL-CEBPA
MTL-CEBPA is the first therapy that specifically up-regulates CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and in solid tumour cancers have been identified as a critical barrier for many therapies to induce clinical responses. In pre-clinical studies MTL‑CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppressive effect in the tumour micro-environment. MTL-CEBPA is currently in clinical development as a combination therapy for the treatment of advanced liver cancer and advanced solid tumour malignancies.

On April 9, 2021 Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIRTM and ADAPTIR-FLEXTM platform technologies, reported that it will present two new posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting, to be held in two virtual sessions – Saturday, April 10th to Thursday, April 15th, 2021 and Monday, May 17th to Friday, May 21st, 2021 (Press release, Aptevo Therapeutics, APR 9, 2021, View Source [SID1234577799]).

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The posters will provide preclinical updates on APVO603 and Aptevo’s newest pipeline candidate, APVO442.

Title: APVO603: A Dual 4-1BB and OX40 bispecific approach utilizing ADAPTIR technology designed to deliver a conditional T cell/NK response against solid tumors (LB173)

Summary: The data to be presented will highlight the potential benefits of dual targeting of 4-1BB and OX40 by APVO603. In vitro data includes demonstration of APVO603’s ability to reduce or reverse the negative effects of T-cell exhaustion and suppressive immune responses by augmenting cytokine production and reducing markers of T-cell exhaustion following repeat stimulation. In preclinical in vivo studies, APVO603 therapy induced a dose-dependent anti-tumor response and significantly increased the survival of mice in a murine bladder cancer model. A non-GLP NHP PK/Tox study was completed and it was found that APVO603 had a favorable safety profile without liver toxicity and a PK profile that supports clinical dosing. CMC activities are in progress and IND-enabling studies are underway to progress the program towards clinical development.

Title: APVO442: A bispecific T cell-engaging candidate utilizing the ADAPTIR-FLEX platform technology with unique properties designed to optimize drug tumor distribution and cytotoxic response against PSMA-expressing solid tumors

Summary: The data to be presented will highlight the unique properties of APVO442, Aptevo’s first molecule utilizing our ADAPTIR-FLEX technology, designed with low affinity, monovalent targeting of CD3 and high affinity, bivalent targeting of PSMA to potentially reduce safety signals and improve efficacy for treatment of a solid tumor. In vitro, APVO442 retains strong binding to tumor cell lines with a range of (high to low) surface PSMA expression, and demonstrates reduced binding to CD3+ T cell lines when compared to higher affinity CD3 binding molecules. In vitro efficacy studies show that, despite lower CD3 binding affinity, APVO442 elicits equivalent T-cell activation, proliferation, and cytotoxicity against PSMA+ tumor cells, while limiting cytokine release, when compared to higher affinity CD3 engaging molecules. In vivo, APVO442 demonstrated a dose-dependent ability to limit tumor burden at responses comparable to a high affinity T-cell engager response in a murine xenograft PSMA+ prostate cancer model. APV0442 retains key manufacturability characteristics of the ADAPTIR platform and preclinical data to support the potential for a beneficial safety and efficacy profile. Continued pre-clinical evaluation and CMC efforts are ongoing to progress APVO442 toward clinical development.

Details of the e-Poster Presentations: The abstracts and the accompanying e-posters will be available in the Virtual Poster Hall to registered attendees from 8:30 am EST on Saturday, April 10th, 2021, until the Virtual Poster Hall closes on Monday June 21st, 2021. Chat and live meeting requests will be available for questions and discussion with the presenters. Details can be found on the AACR (Free AACR Whitepaper) abstract website and will also be posted on the Aptevo Therapeutics website.

On April 9, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported new preclinical data supporting the ongoing development of three of its drug candidates, repotrectinib, TPX-0022 and TPX-0131 (Press release, Turning Point Therapeutics, APR 9, 2021, View Source [SID1234577798]). The findings will be presented this weekend at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, which is convening virtually through April 14.

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For lead drug candidate, repotrectinib, poster presentations will highlight new preclinical combination data with MEK and MEK/Raf inhibitors, as well as repotrectinib’s potency against wildtype and mutant TRKA/B/C as compared to approved TRK inhibitors. The preclinical studies found that repotrectinib combinations with approved MEK inhibitor, trametinib, or investigational MEK/Raf inhibitor, VS-6766, were more effective than single-agent treatment in patient-derived KRAS mutant G12D/V lung and G12D/V/R pancreatic cancer models. Based on the findings and additional preclinical support presented previously, Turning Point anticipates the first cohort of its planned Phase 1/2 TRIDENT-2 study will examine the safety, tolerability, pharmacokinetics, and any early signals of efficacy of repotrectinib in combination with trametinib in patients with KRAS mutant G12D advanced solid tumors.

"We are encouraged by the new preclinical data our research team has generated in support of our ongoing development of repotrectinib, TPX-0022 and TPX-0131," said Athena Countouriotis, M.D., president and CEO. "In particular, our preclinical models continue to suggest that the combination of repotrectinib with MEK inhibitors can suppress mutant KRAS signaling to achieve more potent and durable anti-tumor activity. We look forward to studying this further in the first cohort of our planned TRIDENT-2 combination study.

"In addition, preclinical studies show repotrectinib is highly potent against wild type TRK fusions and is less affected by NTRK resistance mutations than approved therapies, with strong potency in both in vitro and in vivo studies. We look forward to sharing additional clinical data from our TRIDENT-1 study of repotrectinib in the second half of the year."

TPX-0022, MET, SRC, CSF1R Inhibitor
For MET/SRC/CSF1R inhibitor TPX-0022, the company will present preclinical data demonstrating potential utility in combination with immune checkpoint inhibitors. In a syngeneic xenograft tumor model, TPX-0022 treatment downregulated immunosuppressive cytokines, increased anti-tumor M1 macrophages, and enriched levels of CD8+ cytotoxic T cells. TPX-0022 had single agent in vivo efficacy and enhanced the efficacy of an anti-PD-1 inhibitor. With the new data, Turning Point is evaluating a potential additional combination study of TPX-0022 and an anti-PD-1 checkpoint inhibitor. In the second half of 2021, the company plans to provide a clinical data update from the Phase 1 dose finding portion of its ongoing SHIELD-1 study and initiate its planned Phase 1b/2 SHIELD-2 clinical study of TPX-0022 in combination with an EGFR targeted therapy.

TPX-0131, ALK Inhibitor
For its ALK-inhibitor, TPX-0131, Turning Point will present preclinical data showing its potential to cross the blood-brain barrier and its potency against wild type ALK and a broad spectrum of acquired ALK resistance mutations, including the G1202R solvent front mutation, L1196M gatekeeper mutation, and the G1202R/L1196M and /L1198F compound mutations. Turning Point plans to initiate a Phase 1/2 study in patients with ALK-positive TKI-pretreated advanced non-small cell lung cancer in the second quarter of 2021.

AACR plans to make poster presentations available via its website on Saturday, April 10. The four posters to be presented are:

Title: Repotrectinib increases effectiveness of MEK inhibitors in KRAS mutant cancer models
Abstract Number: 1104

Title: Molecular characteristics of repotrectinib that enable potent inhibition of TRK fusion proteins and broad mutant selectivity
Abstract Number: 1119

Title: TPX-0022, a potent MET/SRC/CSF1R inhibitor that modulates the tumor immune microenvironment in preclinical models
Abstract Number: 1444

Title: TPX-0131, a potent inhibitor of wild type ALK and a broad spectrum of both single and compound ALK resistance mutations
Abstract Number: 1469

On April 9, 2021 IntelGenx Technologies Corp. (TSX-V:IGX) (OTCQB:IGXT) ("IntelGenx"), a leader in pharmaceutical films, reported that it is proposing to amend the terms of its 6.0% convertible unsecured promissory notes due June 1, 2021, originally issued by private placement on May 8, 2018 (the "Notes"), to (i) extend the maturity date to October 31, 2024, (ii) change the conversion ratio for conversions at the option of the holders of the Notes from 6,250 fully paid and non-assessable shares of common stock for each U.S.$5,000 aggregate principal amount of the Notes then outstanding to 11,363 fully paid and non-assessable shares of common stock for each U.S.$5,000 aggregate principal amount of the Notes then outstanding, effectively representing a reduction of the conversion price from U.S.$0.80 to U.S.$0.44, and (iii) reduce the trigger price for a conversion at the option of IntelGenx from U.S.$1.40 or greater for 20 consecutive trading days to U.S.$0.88 or greater for 20 consecutive trading days (Press release, IntelGenx, APR 9, 2021, View Source(TSX%2DV%3AIGX),date%20to%20October%2031%2C%202024%2C [SID1234577797]). The proposed amendments are subject to approval of the TSX Venture Exchange and holders holding a majority of the aggregate outstanding principal amount of the Notes.

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An aggregate principal amount of U.S.$1,600,000 of Notes is outstanding as of the date hereof.

On April 9, 2021 Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, reported that David Meline, Chief Financial Officer, and Lavina Talukdar, Senior Vice President & Head of Investor Relations, will participate in a fireside chat at the 20th Annual Needham Virtual Healthcare Conference on April 15th, 2021 at 11:45 a.m. ET.

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A live webcast will be available under "Events and Presentations" in the Investors section of the Moderna website at investors.modernatx.com. A replay of the webcast will be archived on Moderna’s website for 30 days following the presentation.