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 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.

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."