On April 12, 2021 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its collaborators presented positive preclinical data for the combination of TUSC2 immunogene therapy (REQORSA) in combination with chemotherapy and immunotherapies for the treatment of non-small cell lung cancer (NSCLC) (Press release, Genprex, APR 12, 2021, View Source [SID1234577930]). Collaborators also presented positive preclinical data for the use of REQORSA in combination with targeted therapies for the treatment of NSCLC. These data were presented in two presentations at the 2021 American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting. The TUSC2 gene is a tumor suppressor gene and is the active agent in REQORSA.

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"We are pleased to have these positive data that provide further support for the therapeutic potential of REQORSA in combination with immunotherapies and targeted therapies in NSCLC presented before an audience of the world’s leading cancer researchers. These data are particularly encouraging as we look to initiate our upcoming combination Acclaim-1 and Acclaim-2 clinical trials of REQORSA in NSCLC," said Rodney Varner, President and Chief Executive Officer of Genprex. "We know that many patients inevitably develop resistance to immune checkpoint blockade therapy or EGFR-TKI therapy. These data show that REQORSA in combination with immunotherapies and targeted therapies may provide enhanced efficacy in NSCLC that has become resistant to these regimens, offering hope to a large patient population who currently has limited treatment options."

Featured Genprex-supported posters presented at AACR (Free AACR Whitepaper) 21 include:

Oral Presentation
Session:

MS.IM02.02 – Overcoming Resistance in the Tumor Microenvironment: Novel Immunomodulatory Agents

Title:

"TUSC2 immunogene therapy enhances efficacy of chemo-immune combination therapy and induces robust antitumor immunity in KRAS-LKB1 mutant NSCLC in humanized mice"

Poster Number/Channel:

#76/Channel 03

Presentation Date/Time:

April 10, 2021 from 2:50-3:00 p.m. ET

Presenters:

Ismail M. Meraz, Mourad Majidi, RuPing Shao, Feng Meng, Min Jin Ha, Elizabeth Shpall, Jack A. Roth. University of Texas MD Anderson Cancer Center, Houston, TX

Poster Presentation
Session:

PO.ET03.01 – Drug Resistance in Molecular Targeted Therapies

Title:

"Overcoming resistance to osimertinib by TUSC2 gene therapy in EGFR mutant NSCLC"

Poster Number:

#1105

Presentation Date/Time:

April 10, 2021 from 8:30 a.m. – 11:59 p.m. ET

Presenters:

Ismail M. Meraz, Mourad Majidi, RuPing Shao, Lihui Gao, Meng Feng, Huiqin Chen, Min Jin Ha, Jack A

The first presentation, entitled "TUSC2 immunogene therapy enhances efficacy of chemo-immune combination therapy and induces robust antitumor immunity in KRAS-LKB1 mutant NSCLC in humanized mice," showed that the triple combination of chemotherapy, immunotherapy (immune checkpoint blockade) and REQORSA demonstrated strong antitumor efficacy and induced robust antitumor immunity in KRAS-LKB1 (KL)-mutant NSCLC in clinically relevant humanized mice models.

In this study, researchers evaluated the antitumor immune response of a chemo-immunotherapy combination with REQORSA on highly metastatic KL-mutant human lung cancer in humanized mice. Humanized mice were first treated with REQORSA, immunotherapy nivolumab (Opdivo), or the combination. The results showed synergistic antitumor activity with the combination. Next, humanized mice were treated with REQORSA, immunotherapy pembrolizumab (Keytruda), or the combination. When REQORSA was added to the chemotherapy and immune checkpoint blockade combination, metastases regression was significantly greater than either REQORSA, REQORSA and pembrolizumab, or chemotherapy and pembrolizumab treatments.

"KRAS is a frequent genomic driver in lung adenocarcinoma," said Michael Redman, Executive Vice President and Chief Operating Officer of Genprex. "LKB1 (also known as STK11) is a distinct subgroup of KRAS-mutants and is the most prevalent genomic driver of resistance to PD-1 blockade in KRAS-mutant lung cancer."

The second poster, entitled "Overcoming resistance to osimertinib by TUSC2 gene therapy in EGFR-mutant NSCLC," showed that REQORSA in combination with targeted therapy osimertinib (Tagrisso) demonstrated synergistic antitumor efficacy in EGFR mutant osimertinib resistant NSCLC tumors in H1975-OsiR isogenic tumors. Researchers also found that the upregulation of PDK1 was associated with osimertinib resistance.

In this study, researchers developed an osimertinib resistant H1975-OsiR isogenic cell line through continuous exposure to osimertinib. Xenograft tumors from both H1975-parental and H1975-OsiR cells were developed in NSG mice and were treated with osimertinib. Synergistic antitumor activity of REQORSA and osimertinib was found in H1975-OsiR tumors. The combinations showed a robust antitumor effect compared with single agent treatment groups. Reverse phase protein array (RPPA) data showed that PDK1 was significantly upregulated in the REQORSA and osimertinib group when compared with either control, osimertinib alone or REQORSA alone treated H1975-OsiR tumors, indicating that PDK1 may be associated with osimertinib resistance. No PDK1 inhibitor effect was found in the REQORSA treated group, implicating the specific role of PDK1 in osimertinib resistance.

These AACR (Free AACR Whitepaper) presentations and posters have been made available on Genprex’s website at www.genprex.com.

On April 12, 2021 Advaxis, Inc. (Nasdaq: ADXS) (the "Company"), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported it has entered into definitive agreements with two healthcare-focused, institutional investors for the purchase of (i) 17,577,400 shares of common stock , (ii) 7,671,937 pre-funded warrants (the "Pre-Funded Warrants") to purchase 7,671,937 shares of common stock and (iii) registered common share purchase warrants to purchase 11,244,135 shares of common stock (Press release, Advaxis, APR 12, 2021, View Source [SID1234577897]). The Company has also agreed to issue to the investors, in a concurrent private placement, unregistered common share purchase warrants to purchase 14,005,202 shares of the Company’s common stock. Each share of common stock and accompanying common share purchase warrant are being sold together at a combined offering price of $0.7921, and each Pre-funded Warrant and accompanying common warrant are being sold together at a combined offering price of $0.7911, pursuant to a registered direct offering, priced at-the-market under Nasdaq rules. The Pre-Funded Warrants are immediately exercisable, at an exercise price of $0.001, and may be exercised at any time until all of the Pre-Funded Warrants are exercised in full. The registered common share purchase warrants will have an exercise price of $0.70 per share, will be immediately exercisable, and will expire five (5) years from the date of issuance. The unregistered common share purchase warrants will have an exercise price of $0.70 per share, will be exercisable fourteen days after the Company increases its authorized share capital, and will expire five (5) years from their initial exercise date (collectively, the "Offering").

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The Company plans to use the net proceeds from the offering to fund its continued research and development initiatives in connection with expanding its product pipeline including, but not limited to, investment in its ADXS-HOT program and for general corporate purposes. The Company may also use a portion of the net proceeds to acquire or invest in other businesses, products and technologies.

A.G.P./Alliance Global Partners is acting as sole placement agent for the Offering.

The Offering is being made pursuant to an effective shelf registration statement on Form S-3 (File No. 333-226988) previously filed with the U.S. Securities and Exchange Commission (the "SEC"), and an additional registration statement on Form S-3 filed pursuant to Rule 462(b) under the Securities Act, which became effective upon filing on August 30, 2018. A prospectus supplement describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. Electronic copies of the prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022 or via telephone at 212-624-2060 or email: [email protected]. Before investing in this offering, interested parties should read in their entirety the prospectus supplement and the accompanying prospectus and the other documents that the Company has filed with the SEC that are incorporated by reference in such prospectus supplement and the accompanying prospectus, which provide more information about the Company and such offering. Copies of the Supplement, the Base Shelf Prospectus and the Registration Statement may also be obtained from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022 or via telephone at 212-624-2060 or email: [email protected].

No securities regulatory authority has either approved or disapproved of the contents of this press release. This press release is for information purposes only and shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On April 12, 2021 Amphivena Therapeutics, a clinical-stage immuno-oncology company focused on developing immuno-therapeutics that restore anti-cancer immunity, reported translational data for the Company’s lead clinical candidate from a Phase 1 study in patients with advanced solid tumors (Press release, Amphivena Therapeutics, APR 12, 2021, View Source [SID1234577931]). The poster, entitled "MDSC Suppress the T Cell Repertoire and Contribute to a Pathologic Cytokine Milieu in Cancer Patients," (Abstract 528) is presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Virtual Annual Meeting.

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"The translational data we are presenting today at AACR (Free AACR Whitepaper) continue to highlight the unique properties of AMV564 and our broader platform technology. AMV564 relieves immune suppression via MDSC depletion which results in the expansion of anti-tumor T-cells, while attenuating the biological responses that contribute to cytokine release syndrome. These findings are consistent with both the clinical activity and safety profile that we have observed in our phase 1 dose escalation in solid tumor patients, with no CRS at doses of 5 – 50 mcg. As our work advances, we are confident that these data signal an opportunity for AMV564 as a new, safe treatment paradigm for solid tumors," said Victoria Smith, Ph.D., Chief Scientific Officer of Amphivena Therapeutics.

The poster’s authors conclude:

AMV564 selectively depletes M- and G-MDSC with concomitant activation of T cells, thereby relieving systemic immune suppression and preventing pathologic levels of myeloid cytokines
Control of MDSC by AMV564 yields a pro-inflammatory cytokine profile that is favorable for anti-tumor immunity, without excessive production of myeloid cytokines such as IL6 which are associated with cytokine release syndrome (CRS)
Treatment with AMV564 yields significant expansion of the T cell repertoire including T cell clones not detectable at baseline, and expansion of anti-tumor T cells, in cancer patients
Poster Details:

Session Title: Immunomodulatory Agents and Interventions
Session Start Date/Time: Saturday, April 10, 2021, 8:30 AM – 11:59 PM ET
Title: MDSC suppress the T cell repertoire and contribute to a pathologic cytokine milieu in cancer patients
Authors: Sterling C. Eckard, et al.
Abstract: 528

The abstract is available on the AACR (Free AACR Whitepaper) Annual Meeting website, and in addition, the poster is available on the Presentations & Publications page on the Amphivena website.

About AMV564

AMV564 relieves immune suppression via targeted depletion of MDSC and drives T cell activation and polarization to restore anti-cancer immunity. To date, over 90 patients have received AMV564 across three Phase 1 clinical trials for patients with solid tumors, acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS).

On April 12, 2021 Aptus Clinical, as the full service CRO provider for the Phase 1b/2a Cancer Appetite Recovery Study (CAReS), reported that it has assisted Artelo Biosciences in the planning and running of this important study which investigates the potential for ART27.13 (a peripherally synthetic cannabinoid agonist), to alleviate anorexia associated with cancer, a condition with significant unmet need and no licensed treatments (Press release, Aptus Clinical, APR 12, 2021, View Source [SID1234577899]).

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Steve McConchie, CEO at Aptus Clinical said ‘The CAReS study is an important investigation in cancer anorexia, and we are delighted that the partnership we have developed with Artelo has achieved the important milestone of first patient recruited and dosed. We are excited to be working with Artelo in assessing whether ART27.13 can make a difference to patients who are suffering from this distressing condition and improve their quality of life.

Gregory D. Gorgas, President and CEO of Artelo Biosciences commented "Artelo are excited to be starting the CAReS trial investigating ART27.13 in patients who currently have no licensed options to alleviate the devastating condition of cancer-associated anorexia. ART27.13 has already demonstrated significant weight gain potential in patients with chronic back pain who were otherwise healthy, and we look forward to seeing the results when translated into anorexic cancer patients who have suffered significant weight loss."

On April 12, 2021 ONCURIOUS NV, a Belgium-based biotech company focused on developing innovative oncology treatments, reported that encouraging data from a Phase 1 dose escalation study of TB-403 in pediatric subjects with relapsed or refractory medulloblastoma (MB), was presented at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Oncurious, APR 12, 2021, View Source [SID1234577915]).

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The data was presented by Dr. Giselle Sholler, Director, Isabella Santos Foundation Solid and Rare Tumor Program, Chair at Beat Childhood Cancer Research Consortium, and Professor, Paediatric Oncology at the Levine Children’s Hospital in Charlotte, NC.

The Phase 1 trial (ONC-403-001) was an open–label, multi-center, dose escalation study of TB–403 in a total of 15 pediatric subjects – 11 with relapsed or refractory MB, 2 with Ewing Sarcoma (ES) and 2 with alveolar rhabdomyosarcoma (ARMS). The study was conducted in conjunction with the Beat Childhood Cancer Research Consortium, Massachusetts General Hospital and Atrium Health Levine Children’s Hospital.

The study evaluated 4 dose levels of TB-403: 20 mg/kg, 50 mg/kg, 100 mg/kg, and 175 mg/kg. The dose limiting toxicity (DLT) assessment cycle for the study was 28 days with subjects receiving 2 doses of TB-403 at Day 1 and Day 15 respectively. After the DLT period, temozolomide or etoposide could be added to the subject’s treatment regimen.

Evaluations for the response to TB-403 were made at the end of cycle 1 and every 2 cycles thereafter.

The key safety findings from the study were as follows:

TB-403 was safe and well tolerated at all dose levels: no maximum tolerated dose (MTD) was reached
TB-403 exposure of children is in accordance with the exposure of the drug in adults
TB-403 exposure and concentration increased dose-proportionally over the dose range of 20-175 mg/kg

The key response findings were as follows:

At the 3 highest dose levels of TB-403, 7 out of 8 of medulloblastoma patients had stable disease
4 medulloblastoma patients had prolonged stabilization of disease > 100 days
Exploratory biomarker analysis showed a decrease in plasma levels of free placental growth factor (PlGF) to undetectable levels at all doses of TB-403, with no apparent changes in other angiogenic or inflammatory factors.

The results of the Phase 1 study warrant further evaluation of TB-403 in pediatric subjects with relapsed or refractory medulloblastoma (MB).

Dr. Giselle Sholler, Chair at Beat Childhood Cancer Research Consortium, commented: "I am pleased that the Beat Childhood Cancer Research Consortium has been able to play a key role in this important study. The encouraging data that I presented at AACR (Free AACR Whitepaper) show that treatment with TB-403 can produce a clinically meaningful response in a significant number of children with relapsed and refractory medulloblastoma. The encouraging results, in what is a very difficult to treat patient population, warrant further clinical investigation, and we at the Beat Childhood Cancer Research Consortium would be happy to play our role in any such effort."

TB-403 is a humanized monoclonal antibody against PlGF which is expressed in several types of cancer, including medulloblastoma. A paper in Cell (Cell, 152, 1065-76, 2013), highlighted that PlGF plays a role in the growth of medulloblastoma. The paper was based on preclinical research conducted by Prof Rakesh Jain from the Massachusetts General Hospital at Harvard (Boston) and the team of Prof Dr. Peter Carmeliet from the VIB/ KU Leuven.

Prof Dr. Peter Carmeliet from the VIB/ KU Leuven, added, "I am pleased that our preclinical research showing that PlGF plays a key role in the growth of medulloblastoma has been confirmed in this Phase 1 clinical study with TB-403. I look forward to following the further clinical development of this novel PIGF inhibitor and am confident that it has the potential to benefit children suffering from this devastating brain cancer."

Dr. Patrik De Haes, Executive Chairman of Oncurious said, "I would like to thank everyone who has taken part in the execution of this successful study with TB-403, especially the patients and their families. The data that has been generated show that TB-403 could expand the treatment options for children with relapsed and refractory medulloblastoma. Meanwhile, Oncurious’ international patent application, published with a positive indication on the patentability of the combination of TB-403 with etoposide or temozolomide, and expiring as late as 2040, puts Oncurious in a good position to evaluate potential partnering options for future development and manufacturing of TB-403."