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 Onxeo S.A. (Euronext Growth Paris: ALONX; Nasdaq First North Growth Copenhague: ONXEO, a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage Response (DDR), in particular against rare or resistant cancers, reported the result of its capital increase through the issuance of new shares (the "New Shares") with shareholders’ preferential subscription rights (PSR), whose subscription took place from March 19 to March 31, 2021 included in France and from March 19 to March 26, 2021 included in Denmark (Press release, Onxeo, APR 12, 2021, View Source [SID1234580416]).

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The gross amount of the capital increase, including the issue premium, amounted to 9.7 million euros and resulted in the creation of 13,677,125 New Shares, at a subscription price per share of 0.71 euro (5.287 DKK on the basis of an exchange rate of 7.447 DKK for 1 euro on March 9, 2021).

The proceeds from this issue of New Shares are intended to finance primarily the expansion and acceleration of the clinical development of AsiDNA, in particular in combination with other anti-cancer agents.

The Company also intends to:

continue the optimization and preclinical development of new candidates selected on the platON platform,
optimize pharmaceutical development and compound manufacturing operations, and
more generally, finance the Company’s operations.
Judith Greciet, CEO of Onxeo, said: "We would like to thank all our investors, both historical and new, who have contributed to the success of this fundraising. The renewed confidence in our long-term strategy by our two core shareholders, Financière de la Montagne and Invus, as well as by many other shareholders, secures the ramp-up of our development and extends our visibility until the end of 2022. With the funds raised, the Company will accelerate the development of AsiDNA with other clinical trials, notably in non-small cell lung cancer, with a phase 2 study designed to be extended as a potential pivotal trial. The clinical program should also include the United States as part of the acceleration plan. Additionally, we will expand our portfolio with other compounds from our platON platform."

The Board of Directors of Onxeo, in its meeting on April 12, 2021, recorded the amount of subscriptions and decided on the final terms of the capital increase with preferential subscription rights of shareholders decided on March 9, 2021.

RESULT OF THE RIGHT ISSUE

At the end of the subscription period, subscriptions totaled 13,677,125 shares, divided as follows:

6,111,797 New Shares were subscribed on an irreducible basis;
7,565,328 Shares News were requested on a free basis.
As the Company has decided to exercise the extension clause provided for in the 20th resolution of the General Meeting of June 19, 2020 for 4.8% of the initial offer, the new shares applied for on a free basis were fully allocated.

Consequently, the gross amount of the capital increase, including issue premium, amounts to 9,710,758.75 euros and results in the issue of 13,677,125 new shares, at a unit subscription price of 0.71 euros, corresponding to a subscription rate of approximately 104.8%.

The Company’s share capital following the capital increase will amount to 22,998,733.75 euros, divided into 91,994,935 shares with a par value of 0.25 euros each.

The settlement-delivery of the New Shares and their admission to trading on Euronext Growth Paris and Nasdaq First North Growth Copenhagen are scheduled for April 16 and April 19, 2021, respectively.

The New Shares will carry dividend rights and will be traded on the same quotation line as the existing shares (ISIN FR0010095596).

Impact of the issue on the shareholding structure

The following table presents the distribution of capital, to the Company’s knowledge, before and after the completion of the capital increase.

The commitments of the existing shareholders, Financière de la Montagne and Invus Public Equities LP, were fully subscribed for a total amount of 7 million euros, respectively 3 and 4 of which approximately 2.1 million euros were on an irreducible basis and 4.9 million euros on a free basis. The subscriptions of other investors thus amount to about 2.7 million euros.

Actionnaires Number of shares before the issue % of capital and voting rights(1) shares before the issue Number of shares after the issue % of capital and voting rights(1) shares after the issue
Financière de la Montagne 10,462,560 13.36% 14,708,767 15.99%
Invus Public Equities LP 8,397,270 10.72% 14,031,073 15.25%
Free float 59,457,980 75.92% 63,255,095 68.76%
Total 78,317,810 100.00% 91,994,935 100.00%
Theoretical voting rights. All shares have the same voting rights, with the exception of treasury shares held by the Company.
DILUTION

For information purposes, the impact of the issue on the capital ownership of a shareholder holding 1% of the Company’s share capital prior to the issue and who did not subscribe to the issue (calculations based on a number of 78,317,810 shares making up the Company’s share capital at December 31, 2020) is as follows:

Shareholder’s interest (%)
(en euro par action) Non-diluted basis Diluted basis (1)
Before issue of New Shares 1.00 0.95
After issue of 13,677,125 New Shares 0.85 0.81
(1) Taking into account the 4,335,740 options and warrants giving access to the share capital granted and outstanding as of today.

INDICATIVE TIMETABLE OF THE OPERATION

April 16, 2021 Issuance of New Shares – Settlement and Delivery.
April 19, 2021 Admission of the New Shares to trading on Euronext Growth Paris and Nasdaq First North Growth Copenhagen.

Contributors

– Invest Securities acted as Lead Manager and Bookrunner of the transaction.

– Invest Corporate Finance acted as Listing Sponsor.

– Nordea Denmark, a subsidiary of Nordea Bank Abp, Finland, acted as underwriting agent in Denmark.

AVAILABILITY OF THE PROSPECTUS

The Prospectus, having received the approval n°21-063 dated March 9, 2021 from the Autorité des marchés financiers ("AMF"), consists of (i) the Universal Registration Document of Onxeo filed with the AMF on April 27, 2020 under number D.20-0362 (the "Universal Registration Document"), (ii) the Amendment to the Universal Registration Document, filed with the AMF on March 9, 2021 under number D.20-0362-A01, (iii) a Securities Note and (iv) a summary of the Prospectus (included in the Securities note).

Copies of the Prospectus are available free of charge at the registered office of Onxeo, 49, boulevard du Général Martial Valin – 75015 Paris. The Prospectus may also be consulted on the websites of the AMF (www.amf-france.org) and Onxeo (www.onxeo.com) and from the Lead Manager and Bookrunner.

In connection with the opening of the public offering in Denmark, an unofficial translation into English of all the documents constituting the prospectus has also been prepared by the Company. In the event of any discrepancy between the French prospectus and the English translation, the French version will prevail. These documents are also available free of charge at Onxeo’s registered office at 49, boulevard du Général Martial Valin – 75015 Paris and on Onxeo’s website (www.onxeo.com).

Risk Factors

Investors are invited to carefully consider the risk factors detailed in section 3 of the Universal Registration Document, section 2 of the Amendment to the Universal Registration Document and section 2 of the Securities Note. The occurrence of all or part of these risks may have an adverse effect on the Group’s business, financial position, results or ability to achieve its objectives.

On April 12, 2021 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics, reported that the first patient has been dosed in the Phase 1 clinical trial of RTX-321 for the treatment of human papilloma virus (HPV) 16-postive cancers (Press release, Rubius Therapeutics, APR 12, 2021, View Source [SID1234584703]). RTX-321 is an allogeneic, off-the-shelf Red Cell Therapeutic product candidate that is engineered as an artificial antigen-presenting cell (aAPC) with a dual mechanism of action: boosting HPV 16-specific CD8+ T cell responses and promoting broad stimulation of both innate and adaptive immune responses. The Phase 1 clinical trial of RTX-321 is enrolling patients with persistent, recurrent, or metastatic, unresectable, HPV 16-positive cancers, including cervical cancer, head and neck squamous cell carcinoma (HNSCC) and anal cancer.

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"In preclinical studies, the surrogate model of RTX-321 induced a broad immune response and epitope spreading, suggesting that in patients, an effective immune response could be generated against multiple HPV antigens," said Christina Coughlin, M.D., Ph.D., chief medical officer of Rubius Therapeutics. "In patients, RTX-321 may also induce tumor-specific memory, potentially enabling the patient’s own immune system to remember a cancer’s identity, which could lead to long-term protection from tumor recurrence. Based on these findings, we believe that RTX-321 may lead to durable responses in patients with HPV 16-positive cancers."

RTX-321 expresses hundreds of thousands of copies of the costimulatory molecule 4-1BBL, the cytokine IL-12 and an HPV peptide antigen bound to major histocompatibility complex (MHC) class I proteins on the cell surface to mimic human T cell-APC interactions. As part of the manufacturing process, Rubius is producing frozen drug substance for the first time, enabling a truly off-the-shelf cellular therapy product candidate with a potential shelf life of up to several years.

"HPV 16 is the most common high-risk strain of HPV and is known to be associated with various types of cancer, including cervical cancer, head and neck squamous cell carcinoma and anal cancer. For patients with advanced HPV 16-positive cancers, the prognosis remains poor with few treatment options beyond the first-line setting," said Howard A. "Skip" Burris, III, M.D., president, clinical operations and chief medical officer, Sarah Cannon Research Institute. "RTX-321 offers a new potential option to treat these patients by utilizing the body’s own immune system. We look forward to working with Rubius Therapeutics to develop RTX-321 for the treatment of patients with HPV 16-positive cancers."

About HPV 16-Positive Cancers
Human papillomavirus (HPV) 16 is associated with approximately 70 percent of cervical cancers, approximately 40 percent of head and neck squamous cell carcinoma (HNSCC) arising in the oropharynx, approximately 25-40 percent of HNSCC arising in other locations and approximately 80-85 percent of anal cancers. A critical need remains for better treatment options for advanced HPV 16-associated cancers. The prognosis remains poor for patients with metastatic disease with few treatment options beyond the first-line setting.

About the RTX-321 Clinical Trial
Rubius Therapeutics is enrolling patients in a Phase 1 open-label, multicenter, monotherapy dose escalation, first-in-human study of RTX-321 for the treatment of patients that are HLA-A*02:01-positive with persistent, recurrent, or metastatic, unresectable, HPV 16-positive cancers, including unresectable cervical cancer (squamous, adeno, or adenosquamous histology), head and neck squamous cell carcinoma (including of the nasal and oral cavities, larynx, hypopharynx, nasopharynx, and oropharynx) and squamous cell cancer of the anal canal that is not amenable to curative therapy. The purpose of the trial is to determine the safety and tolerability, recommended phase 2 dose and pharmacology, and antitumor activity of RTX-321. For more information about the Phase 1 clinical trial of RTX-321, please visit clinicaltrials.gov (NCT04672980).

About RTX-321
RTX-321 is an allogeneic, off-the-shelf aAPC therapy product candidate that is engineered to induce a tumor-specific immune response by expanding antigen-specific T cells. RTX-321 expresses hundreds of thousands of copies of an HPV peptide antigen bound to major histocompatibility complex (MHC) class I proteins, the costimulatory molecule 4-1BBL and the cytokine IL-12 on the cell surface to mimic human T cell-APC interactions.