On March 20, 2019 Oragenics, Inc. (NYSE American: OGEN), a leader in the development of new antibiotics against infectious diseases and effective treatments for oral mucositis, reported that it has commenced a proposed underwritten public offering of common stock of the Company, together with warrants to purchase shares of common stock (Press release, Oragenics, MAR 20, 2019, View Source [SID1234534524]). In addition, the Company expects to grant the underwriter of the offering, a 30-day option to purchase additional shares of common stock and/or warrants at the public offering price, less underwriting discounts and commissions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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H.C. Wainwright & Co. is acting as sole book-running manager for the offering.

The Company intends to use the net proceeds of the offering to fund its AG013 research, clinical trials, pre-clinical development of the lantibiotics program, and for working capital and general corporate purposes.

The securities described above are being offered pursuant to a shelf registration statement (File No. 333-213321), which was declared effective by the United States Securities and Exchange Commission ("SEC") on September 7, 2016. A preliminary prospectus supplement relating to the offering will be filed with the SEC. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, at the SEC’s website at www.sec.gov. Electronic copies of the preliminary prospectus supplement and accompanying prospectus also may be obtained, when available, from H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, email: [email protected].

Before you invest, you should read the preliminary prospectus supplement and the accompanying prospectus in the registration statement and other documents Oragenics has filed or will file with the SEC for more complete information about Oragenics and the offering.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the Company’s securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On March 20, 2019 Petra Pharma Corporation ("Petra"), a leader in phosphoinositide (PI) signaling pathway inhibition, reported it has secured a global license from Takeda Pharmaceutical Company Limited ("Takeda") to develop, manufacture and commercialize serabelisib and two additional PI3Kα-specific inhibitors (Press release, Petra Pharma, MAR 20, 2019, View Source [SID1234554009]). The agreement grants Petra a license for all human therapeutic uses, except for a subset of undisclosed rare-disease indications, which Takeda had previously out-licensed.

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Petra plans to initiate a Phase 1b/2 study with serabelisib in late 2019 to advance pioneering research and insights in PI signaling pathways with a focus on PIK3CA-mutated solid tumors. The PI3K signaling pathway is a frequently mutated pathway in human cancer.

"Today marks a transformational moment for Petra and a new era in the therapeutic use of PI3K inhibitors. We are pioneering new approaches that have the potential to increase tumor responses with PI3K inhibitors and minimize side effects, with profound clinical implications for patients diagnosed with a PIK3CA-mutated tumor," said President and CEO, Brian O’Callaghan.

Petra’s leading-edge research builds on the recent work of Scientific Co-Founder, Lewis Cantley, Ph.D. (Weill Cornell Medical Center) and his collaborators, whose paper in the August 2018 issue of Nature* identified strategies to disrupt the glucose/insulin feedback loop with the potential to dramatically improve the anti-tumor response.

"Current treatment modalities have been challenging due to an on-target effect of PI3Kα inhibitors causing hyperglycemia and consequent elevation of serum insulin, which can re-activate PI3K in tumors, allowing them to survive," said Dr. Cantley. "The approach Petra is taking disrupts the glucose/insulin feedback loop, which in preclinical models significantly increases anti-tumor efficacy."

This is the first licensing agreement between Petra and Takeda. Financial terms of the agreement were not disclosed.

* Hopkins BD, Pauli C, Du X, et al. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature. 2018;560(7719):499-503.

On March 20, 2019 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM), reported that preclinical data from the novel combination of its CD33 ARC or Antibody Radiation-Conjugate Actimab-A (lintzumab-Ac-225) with venetoclax has been accepted for poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), or AACR (Free AACR Whitepaper), Annual Meeting 2019 (Press release, Actinium Pharmaceuticals, MAR 20, 2019, View Source [SID1234534505]). The data to be presented builds on research by Actinium that demonstrated a synergy between Actimab-A and venetoclax, which resulted in greater cancer cell killing. This research supported the initiation of a Phase 1/2 doublet clinical trial studying Actimab-A and venetoclax and a planned Phase 1/2 triplet combination trial of Actimab-A and venetoclax with a hypomethylating agent, both for patients with relapsed or refractory AML or Acute Myeloid Leukemia. Actinium is conducting these trials with the goal of improving outcomes for patients with the addition of Actimab-A to address patients who do not respond, have suboptimal responses, no longer respond and patients who relapse after treatment with venetoclax.

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Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor jointly developed and marketed by AbbVie and Genentech. BCL-2 is one of several proteins encoded by the BCL2 gene that regulates apoptosis or programmed cell death. MCL-1 is another protein encoded by the BCL2 gene that has been found to be overexpressed in relapsed or refractory AML patients, that prevents apoptosis and promotes resistance to venetoclax which does not bind to MCL-1. It has been observed that MCL-1 levels can be depleted with radiation, but only external radiation was used in these studies. Actinium believes that the targeted internalized radiation from Actimab-A can more effectively deplete MCL-1 levels thereby removing the AML cells’ resistance mechanism and rendering them more susceptible to venetoclax. Actinium has filed a patent on the combination of a targeted alpha-emitting therapeutic such as Actimab-A together with a BCL-2 inhibitor, which includes venetoclax, as a method to treat cancer. The details on Actinium’s poster are as follows:

Title: 225Ac-CD33 Radioimmunotherapy potently increases the sensitivity of resistant acute myeloid leukemia lines to the Bcl-2 inhibitor venetoclax by mediating a reduction in cellular Mcl-1 levels

Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Resistance 5
Session Date and Time: Tuesday Apr 2, 2019 1:00 PM – 5:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 10
Poster Board Number: 13
Abstract Number: 3808

Dr. Dale Ludwig, Actinium’s Chief Scientific Officer said, "We are excited to present new data from this Actimab-A ARC and venetoclax combination to further support our recently initiated clinical study and prior work. We have high confidence in the mechanistic rationale of the Actimab-A and venetoclax combination and are encouraged by the results we have seen thus far. With radiation being used in the treatment of up to 60% of cancer patients and a growing body of literature supporting the synergies of radiation therapy with other modalities, we are motivated to capitalize on numerous opportunities that can leverage our AWE or Antibody Warhead Enabling technology platform to exploit radiation’s synergistic effects. Indeed, our AWE technology platform is a tool for innovation that has the potential to expand our pipeline and facilitate collaborations and partnerships."

Actimab-A delivers the potent alpha-particle emitting radioisotope Ac-225 or Actinium-225 to cells with the CD33 antigen, which is expressed in the vast majority of patients with AML, MDS or Myelodysplastic Syndrome, and 25-35% of patients with Multiple Myeloma, or MM. Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor that is jointly developed and marketed by AbbVie and Genentech that is approved for patients with AML, Chronic Lymphocytic Leukemia, and Small Lymphocytic Leukemia. Actinium has initiated a Phase 1/2 trial that is studying Actimab-A in combination with venetoclax for patients with relapsed or refractory AML and is planning a Phase 1/2 trial that is expected to study Actimab-A and venetoclax with a hypomethylating agent also for patients with relapsed or refractory AML.

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "Our Actimab-A venetoclax combination trials are a strategic priority within our CD33 program that demonstrate our ability to rapidly translate research from our AWE technology platform to our clinical pipeline. Our preclinical data demonstrating a synergy between targeted radiation from Actimab-A and venetoclax, together with Actimab-A’s single agent activity and minimal extramedullary toxicities was well received by investigators, allowing us to develop two distinct clinical trials with this novel combination. As a result, we have created multiple opportunities to advance the treatment of patients with unmet needs with our ARC approach."

On March 20, 2019 Affibody AB and Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) reported a partnership to co-develop ABY-039 for rare Immunoglobulin G (IgG)-mediated autoimmune diseases (Press release, Affibody, MAR 20, 2019, View Source [SID1234575709]).

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Agreement provides opportunity to expand Alexion’s clinical-stage anti-FcRn portfolio with ABY-039
Affibody to receive $25 million upfront payment with potential for additional milestone-dependent and royalty payments, and option for U.S. co-promote
Affibody’s technology offers potential for extended half-life compared to other anti-FcRn therapies and low volume subcutaneous administration
Currently in Phase 1 development, ABY-039 is a bivalent antibody-mimetic that targets the neonatal Fc receptor (FcRn). ABY-039 has been specifically designed to combine Affibody’s protein therapeutics platform (Affibody molecules) and Albumod technology to achieve a long half-life, which, along with its small size provides the potential for less frequent, convenient, at-home subcutaneous administration.

"We believe there is significant opportunity to transform patient care with FcRn-targeted therapies and are thrilled to add a second clinical-stage anti-FcRn medicine to our pipeline with this collaboration," said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. "While clinical development is still early, we are excited by ABY-039’s potential to be an optimal subcutaneous therapy across a number of IgG-mediated diseases, providing patients with the possibility of a convenient self-administered treatment option."

"ABY-039 offers an innovative and novel approach to treating IgG-mediated diseases. Its rapid onset, sustained response, long half-life and potential for low volume administration hold great promise as a self-administered subcutaneous anti-FcRn therapy of choice," said David Bejker, Chief Executive Officer of Affibody. "We look forward to building our partnership with Alexion and leveraging their significant development and commercial experience to accelerate the development of ABY-039. This collaboration is another key step in the evolution of our company that is aligned with our key strategic objectives."

ABY-039 is being evaluated in a Phase 1 study in healthy volunteers. This adaptive, double-blind, placebo-controlled study is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABY-039 and will aid in dose selection for future studies. The companies are assessing potential indications for future development.

Under the terms of the agreement, Alexion will provide Affibody with an upfront payment of $25 million, with the potential for additional development- and sales-based milestones of up to $625 million and tiered low double-digit royalty payments. Alexion will lead joint clinical development of ABY-039 and commercialization activities. Affibody has the option to co-promote ABY-039 in the U.S. and will lead clinical development for an undisclosed indication.

The companies expect to close the transaction in the second quarter of 2019, subject to clearance under the Hart-Scott Rodino Antitrust Improvements Act.

Alexion will discuss the partnership further during Alexion’s Investor Day event and webcast on March 20, 2019.

About FcRn

Antibodies play an important role in a healthy body’s defense by fighting infections from bacteria and other invaders. In autoimmune diseases, however, the body mistakenly attacks itself through the production of pathogenic (disease-causing) antibodies of the Immunoglobulin G (IgG) subtype. Neonatal Fc receptor (FcRn) rescues IgGs from lysosomal degradation by binding them to endosomes and returning them to the bloodstream. This helps prolong the half-life of IgG. In healthy individuals, this function contributes to a normal immune response. In many autoimmune conditions, however, FcRn prevents lysosomal degradation of pathogenic IgGs associated with driving the disease. Therefore, blocking the FcRn-IgG interaction has the potential to drive degradation of IgG within cells and rapidly reduce circulating pathogenic IgG.

About ABY-039

ABY-039 is a novel anti-FcRn antibody-mimetic, which has been specifically designed to utilize the advantages of Affibody’s technology platform to differentiate from competing antibody and Fc-based approaches. ABY-039 is a small protein ligand (~19 kDa, approximately an eighth of the size of an antibody) and has an in vivo half-life exceeding that of antibody-based approaches.

On March 20, 2019 4SC AG (4SC, FSE Prime Standard: VSC) reported the financial results for the financial year ended 31 December 2018, presenting all material reporting period developments and provides an outlook for 2019. The full report is available at 4SC’s website (Press release, 4SC, MAR 20, 2019, View Source [SID1234534507]).

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Key highlights of 2018 and 2019 YTD

4SC continued to make solid progress on clinical development of both resminostat and domatinostat (4SC-202)
More than two thirds of patients recruited for pivotal RESMAIN study of resminostat in advanced-stage cutaneous T-cell lymphoma (CTCL); positive safety outcomes to date
Phase II study of resminostat plus S-1 chemotherapy versus S-1 chemotherapy plus placebo as second-line treatment in Japanese patients with biliary tract cancer initiated by Yakult Honsha Co., Ltd. (Yakult Honsha), 4SC’s development partner for resminostat in Japan
Completed second dose cohort of Phase Ib/II study SENSITIZE of domatinostat in combination with pembrolizumab in advanced-stage melanoma; positive safety outcomes to date; third dose cohort started
Initiated investigator-initiated Phase II study EMERGE of domatinostat in combination with avelumab in microsatellite-stable gastrointestinal tumors
Published preclinical data on combination of domatinostat with either chemotherapy or several immunotherapeutic agents leading to evaluation of further clinical combination trials
Strengthened patent protection for Hedgehog/GLI signaling inhibitor 4SC-208 in the U.S., China, Japan, Singapore, Australia and New Zealand.
Received milestone payments from several partnered programs.
Jason Loveridge, Ph.D., CEO of 4SC, said: "4SC continues to make excellent progress with the development of our portfolio of drug candidates.

We expect that the two ongoing clinical trials of domatinostat will provide clinical evidence to further support the efficacy of domatinostat in patients that do not benefit from immunotherapeutic treatment with checkpoint inhibitors (SENSITIZE study, melanoma) or in a historically checkpoint inhibitor non-responsive indication (EMERGE study, microsatellite-stable gastrointestinal cancer). Taken together, we expect these studies to drive initiation of a pivotal clinical study of domatinostat in the aggressive rare skin cancer Merkel-cell carcinoma.

For resminostat, we expect to enroll sufficient patients in the pivotal RESMAIN study in 2019 to observe the required 125 events to unblind the study. Should the trial prove positive, we plan to submit applications for marketing approval of resminostat in CTCL in Europe, and potentially the U.S., and Yakult Honsha will submit in Japan. If approved, resminostat would be the first histone deacetylase inhibitor approved for CTCL in Europe and the first and only drug approved for maintenance therapy in this indication in either Europe, Japan or the U.S.

The main goal of all our activities is to create significant benefit for patients and value for our shareholders by bringing resminostat and domatinostat to market as soon as possible."

Business outlook

Top-line data of the pivotal RESMAIN study expected in H1 2020.
Results of Yakult Honsha’s Phase II study of resminostat in biliary tract cancer to be available by mid-2020.
SENSITIZE study expected to complete in H1 2019.
Safety data of EMERGE expected in Q2 2019 and early efficacy data in H2 2019
Expand clinical development for domatinostat and initiate potentially pivotal study in Merkel-cell carcinoma
Cash balance development in full year 2018 and financial forecast

As of 31 December 2018, 4SC holds cash balance/funds of €25.0 million, as compared to €41.3 million as of 31 December 2017. The average monthly use of cash from operations in 2018 was €1.357 million (2017: €0.723 million), which is within the €1.3 million to €1.5 million forecast in the previous Q3 announcement. The increase of the monthly use of cash and the decrease in cash balance/funds in 2018 was mainly driven by investments in the ongoing clinical studies RESMAIN and SENSITIZE.

Taking into account the current financial planning and the intended operating activities, the Management Board estimates that current funds should be sufficient to finance 4SC for the next twelve months. For 2019, 4SC is expecting an average monthly use of cash from operations of between €1.4 million and €1.6 million. For 2019, 4SC expects the net loss to be similar to 2018. 4SC is expecting to report similar annual net losses, with almost identical functional cost allocations in the short to medium term future as well.

Conference call

Investors, financial analysts, and journalists interested in participating in the conference call on the annual results 2018 can access via the telephone numbers stated below. Please join the event conference 5-10 minutes prior to the start time. You will be asked to provide your name, company and location as well as the access code.

Date: 20 March 2019
Time: 3 pm CET (10 am ET)
Phone Numbers: +49 (0)32 22109 8334 (Germany)
+44 (0)20 3936 2999 (United Kingdom)
+1 845 709 8568 (USA)
Joining by web (free of charge): www.incommuk.com/customers/online
Access Code: 802724

A presentation document supporting the conference call will be available earlier on the same day at 4SC’s website. After the event, a replay can be accessed from there as well.