On June 22, 2020 Ascendis Pharma A/S (Nasdaq: ASND), a biopharmaceutical company that utilizes its innovative TransCon technologies to address unmet medical needs, reported the presentation of preclinical data for TransCon IL-2 β/γ, an oncology product candidate designed to provide sustained systemic release of a receptor-biased IL-2 (IL-2 β/γ), at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II from June 22 to June 24, 2020 (Press release, Ascendis Pharma, JUN 22, 2020, View Source [SID1234561294]).

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"Our preclinical results have demonstrated that TransCon IL-2 β/γ selectively binds and activates the IL-2 β/γ receptor and provides sustained and long-lasting exposure. By applying our TransCon technology to this clinically validated cytokine, we have overcome the two most significant limitations of IL-2 therapy, improving both the receptor-binding properties and the pharmacokinetic profile," said Juha Punnonen, M.D., Ph.D., Ascendis Pharma’s Senior Vice President and Head of Oncology. "Based on the promising preclinical results we’ve seen with our TransCon IL-2 β/γ and TransCon TLR7/8 Agonist product candidates, we believe our TransCon technologies – which enable systemic and long-acting intratumoral administration – have the potential to improve treatment outcomes in cancer patients. We look forward to our first Investigational New Drug application, or similar, in oncology later this year for TransCon TLR7/8 Agonist, followed by a planned filing for TransCon IL-2 β/γ in 2021."

TransCon IL-2 β/γ is a novel long-acting prodrug of IL-2 β/γ designed to address limitations of alternative IL-2 treatments, including aldesleukin, which has been available since the 1990’s as a treatment for advanced kidney cancer and advanced melanoma. TransCon IL-2 β/γ is designed with a parent drug that selectively binds and activates the IL-2Rβ/γ. By applying the innovative TransCon technology platform, preclinical data also showed that TransCon IL-2 β/γ demonstrated a long in vivo half-life of approximately 32 hours, expected to support potential dosing of every three weeks in patients. Preclinical results show a single dose of TransCon IL-2 β/γ selectively expanded lymphocyte counts (CD8+ T cells and NK cells) in non-human primates, with minimal signs of systemic inflammation (IL-5 and IL-6 markers) or endothelial cell damage (E-Selectin and VCAM-1 markers) and no dose-limiting toxicities.

Presentation Details

American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II

Title Date/Time
P4507: TransCon IL-2 β/γ: a novel long-acting prodrug of receptor-biased IL-2 designed for improved pharmocokinetics and optimal activation of T cells for the treatment of cancer Monday, June 22, 2020

8:45 a.m. Eastern

The poster is available on the company’s website under Selected Publications in the Pipeline section:

View Source

About TransCon Oncology Programs

Ascendis Pharma is developing potentially best-in-class oncology therapies by applying its TransCon technologies for systemic and intratumoral administration to clinically validated pathways in order to improve efficacy and reduce systemic toxicity. Multiple oncology programs are currently in preclinical evaluation.

About TransCon Technology

TransCon refers to "transient conjugation." The proprietary TransCon platform is an innovative technology to create new therapies that are designed to potentially optimize therapeutic effect, including efficacy, safety and dosing frequency. TransCon molecules have three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic conditions (e.g., pH and temperature) initiate the release of the active, unmodified parent drug in a predictable manner. Because the parent drug is unmodified, its original mode of action is expected to be maintained. TransCon technology can be applied broadly to a protein, peptide or small molecule in multiple therapeutic areas, and can be used systemically or locally.

On June 22, 2020, Cue Biopharma, Inc. (the "Company") reported that it entered into an At-The-Market Equity Offering Sales Agreement (the "Sales Agreement") with Stifel, Nicolaus & Company, Incorporated, as agent ("Stifel"), pursuant to which the Company may offer and sell, from time to time through Stifel, shares of its common stock, par value $0.001 per share (the "Common Stock"), for aggregate gross proceeds of up to $40.0 million (the "Shares") (Filing, 8-K, Cue Biopharma, JUN 22, 2020, View Source [SID1234561313]). The offer and sale of the Shares will be made pursuant to a shelf registration statement on Form S-3 and the related prospectus (File No. 333-239357) that became effective on June 22, 2020, as supplemented by a prospectus supplement dated June 22, 2020 and filed with the Securities and Exchange Commission pursuant to Rule 424(b) under the Securities Act of 1933, as amended (the "Securities Act").

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Pursuant to the Sales Agreement, Stifel may sell the Shares in sales deemed to be "at-the-market" equity offerings as defined in Rule 415 promulgated under the Securities Act, including sales made directly on or through the Nasdaq Capital Market. If agreed to in a transaction notice, the Company may sell Shares to Stifel as principal, at a purchase price agreed upon by Stifel and the Company. Stifel may also sell Shares in negotiated transactions with the Company’s prior approval. The offer and sale of the Shares pursuant to the Sales Agreement will terminate upon the earlier of (a) the issuance and sale of all of the Shares subject to the Sales Agreement or (b) the termination of the Sales Agreement by Stifel or the Company pursuant to the terms thereof.

The Company has agreed to pay Stifel a commission of up to 3.0% of the aggregate gross proceeds from any Shares sold by Stifel and to provide Stifel with customary indemnification and contribution rights, including for liabilities under the Securities Act. The Company also will reimburse Stifel for certain specified expenses in connection with entering into the Sales Agreement. The Sales Agreement contains customary representations and warranties and conditions to the placements of the Shares pursuant thereto.

A copy of the Sales Agreement is filed as Exhibit 1.1 to this Current Report, and the description of the terms of the Sales Agreement is qualified in its entirety by reference to such exhibit. A copy of the opinion of K&L Gates LLP relating to the legality of the issuance and sale of the Shares is attached as Exhibit 5.1 hereto.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the Shares, nor shall there be any offer, solicitation, or sale of the Company’s Common Stock in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On June 22, 2020 OncoSec Medical Incorporated (the "Company" or "OncoSec") (Nasdaq: ONCS), a company developing late-stage intratumoral cancer immunotherapies, reported that new data further demonstrating the power of OncoSec’s next-generation interleukin-12 (IL-12) plasmid (TAVOPLUS) therapeutic when combined with a T cell stimulator (TAVOPLUS-CD3) or an enhanced chemokine gradient (TAVOPLUS-CXCL9) (Press release, OncoSec Medical, JUN 22, 2020, View Source [SID1234561329]). These product candidates, coupled with the new low-voltage electroporation gene delivery system, represent a promising approach for treating patients with a variety of solid tumors. The data were presented today during two late-breaking poster presentations at the American Association for Cancer (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II being held from June 22-24, 2020.

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"Multiple studies have used intratumoral plasmid IL-12 (TAVO) to treat solid tumor indications with a demonstrable clinical benefit due to this cytokine’s ability to drive deep and durable immune responses," said Christopher Twitty, Ph.D., OncoSec’s Chief Science Officer. "The new preclinical data exhibited in both AACR (Free AACR Whitepaper) presentations highlights the evolution of OncoSec’s IL-12-based platform. Incorporation of a chemokine gradient and a polyclonal T cell stimulator with the enhanced IL-12 backbone of TAVOPLUS holds significant potential in the treatment of solid tumors. We believe these data provide a strong rationale for filing an Investigational New Drug application and we are excited to advance TAVOPLUS into clinical development."

The following posters were presented during the session titled, "Late-Breaking Research: Immunology 2":

Title: "Intratumoral electroporation of plasmid-encoded IL-12 and membrane-bound anti-CD3 increases tumor immunogenicity and augments the function of T cell subsets"
Poster Number: 14
Abstract Number: LB-390

Study Highlights:

Compared to IT-tavo-EP, TAVO+-αCD3 enhances T cells engagement with tumor cells and augments T cell killing function in preclinical cancer models by:

Increasing expressor memory T cells, which may extend anti-tumor response from treatment.
Increasing activated T cells in peripheral blood, which may enhance anti-tumor response throughout the body.
Increasing antigen specific T cells anti-tumor activity, which leads to enhanced cancer cell recognition by T cells.
Restoring the exhausted, non-active T cells’ anti-tumor activity, which leads to re-energized cancer cell killing activity.
Title: "Amplification of the CXCR3/CXCL9 axis via intratumoral electroporation of CXCL9 synergizes with IL-12 gene therapy (TAVO) to elicit robust anti-tumor immunity"
Poster Number: 20
Abstract Number: LB-396

Study Highlights:

Data demonstrated that IL-12, in concert with CXCL9 (a potent chemokine), leads to brisk infiltration of T cells and efficient remodeling of the tumor microenvironment, making tumors more susceptible to treatment.
This new product candidate thus builds upon OncoSec’s plasmid based immunotherapeutic platform by augmenting the effects of IL-12 with the inclusion of CXCL9.
Study showed that combining intratumoral TAVO with a DNA-encoded, locally secreted CXCL9, significantly improves anti-PD1 response, thus providing an approach to extend the benefit of PD-1 blockade to more patients.
The full abstracts presented at the AACR (Free AACR Whitepaper) Virtual Meeting II are available online at www.aacr.org and the posters are available on OncoSec’s website at www.oncosec.com.

On June 22, 2020 Calidi Biotherapeutics, Inc., a clinical-stage biotechnology company at the forefront of oncolytic virus-based immunotherapies for cancer, reported that data from clinical studies on their oncolytic agent, CAL1 vaccinia virus, and stem cell delivery system will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting II, which will be held in virtual format June 22 through June 24, 2020, due to COVID-19 concerns (Press release, Calidi Biotherapeutics, JUN 22, 2020, View Source [SID1234561345]).

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Calidi’s respective e-poster presentations will highlight findings from translational research on the potential use of the CAL1 vaccinia virus, a version of the ACAM2000 smallpox vaccine delivered via an allogeneic adipose-derived mesenchymal stem cell (MSC) system, as well as insights from clinical trials analyzing the potential use of Calidi’s autologous SVF delivery platform to modulate innate and adaptive immunity in patients with solid tumors and hematological malignancies.

CAL1 was evaluated for abilities to safely replicate and selectively kill cancer cells, to be genetically modified (generating next generation armed-oncolytic viruses) without affecting its natural tumor selectivity, and to determine if its anti-tumor effects can be enhanced and protected from inactivation by immune system response when delivered via Calidi’s off-the-shelf MSC platform. The modified vaccinia virus strain demonstrated efficacy as an oncolytic agent, exhibiting heightened therapeutic capacity when loaded into adipose-derived mesenchymal stem cells to create Calidi’s SuperNova (SNV) product.

Calidi’s study on the immunomodulatory potential of vaccinia virus delivered by autologous SVF-derived cells expanded on their recent first-in-human Phase I clinical trial, which confirmed the safety and feasibility of their approach for improving virus delivery and tumor targeting. This study establishes a timeline of treatment-related immunological changes, identifies potential immunological correlations with continued amplified oncolytic therapy, and provides insights into the role of interpatient immunological variability and future oncolytic virotherapy evaluation.

Both abstracts indicate significant advantages and fundamental rationale for the development of vehicles like Calidi’s cell-based delivery platform (View Source), designed to protect and potentiate oncolytic viruses by circumventing innate and adaptive immune barriers, resulting in enhanced oncolytic virotherapy.

AACR presentation details are as follows:

Abstract 6542: CAL1 vaccinia virus as oncolytic agent and potential use of cell-based platform to enhance its therapeutic effects
Date: June 22, 2020, from 9:00 AM to 6:00 PM

Abstract 4473: Evaluation of the potential of oncolytic vaccinia virus delivered by autologous SVF to modulate innate and adaptive immunity in patients with diverse solid and hematological malignancies
Date: June 22, 2020, from 9:00 AM to 6:00 PM

on June 22, 2020 twoXAR Pharmaceuticals, a drug discovery and development company focused on bringing first-in-class small molecules to market, reported that preclinical data for its investigational treatment TXR-311 with a novel MOA demonstrated significant efficacy and good tolerability in in vivo studies for the potential treatment of hepatocellular carcinoma (HCC), with results comparable to sorafenib, today’s standard-of-care (Press release, TwoXAR, JUN 22, 2020, View Source [SID1234561361]). The data was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II. The full poster and accompanying audio of the data is available at www.twoxar.com.

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"We are pleased that our TRX-311 in vivo data was selected for presentation at AACR (Free AACR Whitepaper). This study is another demonstration that our approach to drug discovery is effective in identifying novel molecules that have high likelihood of showing positive safety and efficacy signals in preclinical studies," stated Andrew A. Radin, co-founder and CEO of twoXAR. "We are thrilled with the progress of our HCC clinical program thus far and look forward to advancing additional drug candidates in disease areas with similar unmet needs."

HCC is a complex and heterogenous tumor and the most common type of primary liver cancer. It is difficult to diagnose and treat, with poor survival. It is most commonly associated with underlying chronic liver disease, including hepatitis and alcoholic and non–alcoholic steatohepatitis (NASH).

"While we have some beneficial treatments for hepatocellular carcinoma, this tumor type is a growing problem worldwide and more options are needed," said Dr. Ghassan K. Abou-Alfa, MD, medical oncologist at Memorial Sloan Kettering. "These early results are interesting and exciting because they showed safety and efficacy comparability against sorafenib but with a completely novel mechanism of action."

In validation studies, TRX-311 demonstrated greater activity and selectivity in killing HCC tumor cells than standard of care, sorafenib, and significantly inhibited growth in two HCC patient-derived xenograft (PDX) tumor models. TRX-311 also demonstrated in vivo efficacy comparable to sorafenib with good tolerability.

As part of a larger oncology drug discovery program, twoXAR identified 10 novel MOAs each for HCC and pancreatic ductal adenocarcinoma (PDAC) through its AI-driven drug discovery approach that builds an in-silico disease model using multiple sets of biological, clinical and chemical data. TRX-311 showed the most promising results and was chosen to proceed into lead optimization studies for HCC. TRX-311 also showed in vitro activity at low µm concentrations in PDAC cancer cells.

About Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) occurs most often in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC is a multifactorial disorder and does not cause symptoms in the early stage, which often leads to a delay in diagnosis. The exact cause of HCC is not fully understood.