On October 24, 2017 GT Biopharma Inc. (OTCQB: GTBP and Euronext Paris GTBP.PA) reported the FDA has accepted the transfer of IND 136205 Change of Sponsor from the University of Minnesota to GT Biopharma for a commercial IND of OXS-3550 (anti-CD16-IL-15-anti-CD33); a first of its kind, single-chain, tri-specific NK cell engager (TriKE) (Press release, GT Biopharma , OCT 24, 2017, View Source [SID1234539537]).

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OXS-3550 TriKE technology was developed by researchers at the University of Minnesota Masonic Cancer Center. As demonstrated in non-clinical models, this targeted immunotherapy directs immune cells to kill cancer cells while diminishing drug-related toxicity.

Several months ago, the GT Biopharma TriKE platform technology received funding from the University of Minnesota’s National Institution of Health (NIH) REACH award. This award is given by the NIH to support technology that is promising for commercial success.

The TriKE platform technology can be viewed as a protein version of CAR-T. However, unlike traditional CAR-T platforms like Kite Pharma (KITE) and Juno Therapeutics (JUNO), TriKEs are not an expensive cell therapy currently only available to treat liquid tumors. It is anticipated that TriKEs will be a therapeutic option for a much larger portion of the cancer population at a fraction of the cost. TriKEs are an antibody platform that can be tailored to treat any form of cancer, liquid or solid tumors.

The TriKE platform focuses on Natural Killer (NK) cells, a type of white blood cell, which plays a major role in the rejection of tumor and virally infected cells. NK cells are an important component of the innate immune system and are critical in killing cancer cells.

The TriKE IND (OXS 3550) will focus on AML, the most common form of adult leukemia with 21,000 new cases expected in 2017 alone (American Cancer Society). These patients will require frontline therapy, usually chemotherapy including cytarabine and an anthracycline, a therapy that has not changed in over 40 years. Also, about half will have relapses and require alternative therapies. In addition, about 13,000 new cases of myelodysplastic syndrome (MDS) are diagnosed each year and there are minimal treatment options (Siegel et al, 2014). At a minimum, OXS-3550 can be expected to serve as a relatively safe, inexpensive, and easy to use therapy for resistant/relapsing AML. From a biologic standpoint, it could also be combined with chemotherapy as frontline therapy.

The University of Minnesota’s Deputy Director of the Masonic Cancer Center, Dr. Jeff Miller said, "We have focused on NK cell therapy for the past 20 years at the University of Minnesota Masonic Cancer Center. While promising, limitations of NK cell therapy include their lack of specificity and the fact that they may be suppressed by the tumor microenvironment. The design of the TriKE is intended to overcome both limitations by making NK cells antigen specific and providing IL-15 as an important activation co-stimulus."

GT Biopharma Chief Medical officer (CMO) Dr. Raymond Urbanski said, "Cancer treatment continues to move towards immunotherapy and the TriKE platform is a powerful new approach. It is the protein version of CAR-T without the excessive resource demands, expense and risk. Our current TriKE, OXS-3550, can be given as a convenient IV infusion. The commercial IND allows us to establish the safety of the TriKE which can then be administered on an outpatient basis."

GT Biopharma Chief Executive Officer (CEO) Dr. Kathleen Clarence-Smith said, "TriKEs hold great promise in treating a number of liquid and possibly solid tumors; the IND transfer to GT Biopharma will allow for faster development and earlier delivery to patients who are in great need of better therapies."

GT Biopharma Executive Chairman Anthony J. Cataldo said, "During 2017 we have continued to accomplish our goals. This is another major milestone for our shareholders. We are continuing with our stated efforts to up-list to NASDAQ."

About the TriKE: TriKE CD16/IL15/CD33 focuses on NK cell cancer-killing activity which is expected to be increased by bringing the NK cells in close proximity to the cancer cells. This is achieved by "engagers" (linkers) that bind to CD16 on the surface of NK cells and bind specific proteins (such as CD33) on the surface of cancer cells, thus linking the NK cell to the cancer cell. The inclusion of a modified Interleukin-15 (IL-15), a peptide that activates NK cells, in the "engager" further increases NK cancer-cell killing capabilities and improves their function in the tumor microenvironment (Vallera et al,2016). The TriKE platform consists of "engagers" to which a modified IL-15 has been added.

On October 23, 2017 ADC Therapeutics (ADCT), an oncology drug discovery and development company that specializes in the development of proprietary Antibody Drug Conjugates (ADCs) targeting major cancers, reported that it has raised $200 million through a private placement (Press release, ADC Therapeutics, OCT 23, 2017, View Source [SID1234521080]). The financing was oversubscribed and supported by both existing and new investors, including Auven Therapeutics, Redmile, the Wild Family Office and AstraZeneca.

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The proceeds will be used to progress ADCT-301 and ADCT-402 into planned registrational trials in 2018. Both candidates are currently in four clinical studies in important sub-types of lymphoma and leukemia. ADCT will also advance ADCT-301 into a combination study for solid tumors. Further it will allow the Company to continue the development of the Phase I study of ADCT-502 in patients with advanced solid tumors with HER2 expression, to file INDs for ADCT-602 and ADCT-601, and to progress a pipeline of pre-clinical ADC programs. ADCT expects to have a total of eight programs in clinical development within 18 months.

Dr. Chris Martin, CEO of ADCT, said: "With more than 250 patients dosed, and encouraging data to be presented at the upcoming congress of the American Society of Hematology (ASH) (Free ASH Whitepaper), this financing is a key step in our strategy and will enable us to accelerate our lead programs and to continue to develop our pipeline. This transaction also reflects the potential value to patients of rapidly developing these active drugs as stand alone and combination therapies. We continue to grow our pipeline of proprietary antibody-drug conjugates in important hematological and solid tumor indications both on our own and in partnerships."

ADCT is focused on the development of proprietary ADCs incorporating highly potent pyrrolobenzodiazepine (PBD)-based warheads. ADCT’s clinical and preclinical programs target major types of both hematological malignancies and solid tumours. Since inception in 2012, the Company has raised $455 million to advance its pipeline of proprietary ADCs. The Company has four PBD-based antibody drug conjugates in six ongoing Phase Ia and Ib clinical trials in the USA and in Europe.

On October 23, 2017 AstraZeneca and Merck (NYSE:MRK), known as MSD outside the U.S. and Canada, reported that they have submitted a new drug application (NDA) to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) for the use of LYNPARZA (olaparib) tablets in unresectable or recurrent BRCA-mutated breast cancer, with a decision expected in the second half of 2018.

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The Japan NDA is based on the positive results from the Phase III OlympiAD trial published in the New England Journal of Medicine.

This is the second NDA for LYNPARZA in Japan where the medicine is currently under review for use in ovarian cancer, with a PMDA decision for this indication anticipated in the first half of 2018.

LYNPARZA tablets are currently being tested in a range of tumor types in addition to ovarian and breast, including prostate and pancreatic cancers.

IMPORTANT SAFETY INFORMATION

DOSING AND ADMINISTRATION

To avoid substitution errors and overdose, do not substitute LYNPARZA (olaparib) tablets with LYNPARZA capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. Recommended tablet dose is 300 mg, taken orally twice daily, with or without food. Continue treatment until disease progression or unacceptable toxicity. For adverse reactions, consider dose interruption or dose reduction.

WARNINGS AND PRECAUTIONS

There are no contraindications for LYNPARZA.

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some of these patients also had a history of previous cancer or bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt treatment with LYNPARZA and initiate prompt investigation. Discontinue LYNPARZA (olaparib) if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving the final dose.

ADVERSE REACTIONS—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), and decreased appetite (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: decrease in hemoglobin (90%), increase in mean corpuscular volume (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA (olaparib) in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, be aware of a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Lactation: No data are available regarding the presence of olaparib in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild hepatic impairment (Child-Pugh classification A). There are no data in patients with moderate or severe hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr 51-80 mL/min). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

Please see complete Prescribing Information, including Patient Information (Medication Guide)

About OlympiAD
OlympiAD is a randomized, open-label, multicenter phase 3 trial assessing the efficacy and safety of LYNPARZA (olaparib) tablets (300mg twice daily) compared to ‘physician’s choice’ chemotherapy (capecitabine, vinorelbine, eribulin) in 302 patients with HER2-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations, which are predicted or suspected to be deleterious. The international trial was conducted in 19 countries from across Europe, Asia, North America and South America.

About LYNPARZA (olaparib)
LYNPARZA was the first FDA-approved oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumor DNA damage response (DDR) pathway deficiencies to potentially kill cancer cells. Specifically, in vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.

LYNPARZA is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.

About Metastatic Breast Cancer
Approximately one in eight women are diagnosed with breast cancer in the U.S. Of these patients, approximately one-third are either diagnosed with or progress to the metastatic stage of the disease. Despite treatment options increasing during the past three decades, there is currently no cure for patients diagnosed with metastatic breast cancer. Thus, the primary aim of treatment is to slow progression of the disease for as long as possible, improving or at least maintaining, a patient’s quality of life.

About Germline BRCA Mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

About the AstraZeneca and Merck Strategic Oncology Collaboration
On July 27, 2017, AstraZeneca and Merck & Co., Inc., announced a global strategic oncology collaboration to co-develop and co-commercialize AstraZeneca’s LYNPARZA (olaparib), the world’s first and leading PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. The collaboration is based on increasing evidence that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of tumor types. Working together, the companies will jointly develop LYNPARZA and selumetinib in combination with other potential new medicines and as a monotherapy. Independently, the companies will develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

On October 23, 2017 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that it has entered into definitive purchase agreements with certain accredited investors to purchase 5,270,934 shares of its common stock, at a purchase price per share of $1.34375 in a registered direct offering priced at the market (Press release, OncoSec Medical, OCT 23, 2017, View Source [SID1234521081]). Additionally, OncoSec has also agreed to issue to the investors unregistered warrants to purchase up to an aggregate of 3,953,200 shares of common stock at an exercise price of $1.25 per share for a term of 5.5 years. The warrants are immediately exercisable on the date of issuance. The offering is expected to close on or about October 25, 2017, subject to the satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The gross proceeds of the offering are expected to be approximately $7.1 million. Net proceeds, after deducting the placement agent’s fee and other estimated offering expenses payable by OncoSec, are expected to be approximately $6.2 million. OncoSec intends to use the net proceeds from this offering for working capital and general corporate purposes, including primarily for the PISCES/KEYNOTE-695 study, and for other clinical, research and development activities.

The shares of common stock (but not the warrants or the shares of common stock underlying the warrants) are being offered by the Company pursuant to a "shelf" registration statement on Form S-3 that was filed and declared effective by the Securities and Exchange Commission ("SEC") and the base prospectus contained therein (File No. 333- 213036). The offering of the shares of common stock will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. The warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the shares of common stock underlying the warrants, have not been registered under the Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws.

A prospectus supplement and accompanying base prospectus relating to the shares of common stock being offered will be filed with the SEC. Copies of the final prospectus supplement and accompanying base prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 4th Floor, New York, NY 10022, by phone at 646-975-6996 or e-mail at [email protected].

This press release 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 an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On October 23, 2017 Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) ("Prometic") reported that it has entered into a binding letter of intent to secure a USD $80 million (CAD $100 million) line of credit (the "Credit Facility") from Structured Alpha LP ("SALP"), an affiliate of Peter J. Thomson’s investment firm, Thomvest Asset Management Inc (Press release, ProMetic Life Sciences, OCT 23, 2017, View Source [SID1234521278]). The first two tranches can be drawn within fifteen days of closing, with each additional tranche becoming available on a monthly basis thereafter. Any amount drawn from the Credit Facility will bear interest of 8.5% per annum and will be repayable within two years from the entering into the Credit Facility.

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Stefan Clulow, Managing Director and Chief Investment Officer of Thomvest Asset Management Inc. said, "We are pleased to extend this Credit Facility to the company, at what is clearly a pivotal time. Prometic is on the cusp of delivering against several key milestones, and this drawdown facility is designed to provide a flexible bridge to those events".

"The scale and structure of this facility provides us with significant operational and financial flexibility to continue with our ongoing negotiations to monetize certain corporate assets. Furthermore, the existing strong relationship with Thomvest allows us to leverage our current security package to its full effect", said Mr. Pierre Laurin, Prometic’s President and Chief Executive Officer. "The flexibility provided by this Credit Facility also means the company can draw only when required which allows our team to focus on closing value-enhancing initiatives and create significant enterprise value for Prometic and its stakeholders".

Commenting on the transaction, Mr. Bruce Pritchard, Prometic’s Chief Operating Officer and Chief Financial Officer added, "We are confident that by securing this credit facility, the company now has the means to fund itself, with limited dilution to existing shareholders, to the point where it will see revenues flowing from its sales of plasminogen (RyplazimTM), as well as from asset monetization events".

As partial consideration for establishing the Credit Facility, Prometic will grant Structured Alpha LP an initial 10 million warrants with an exercise price of CAD $1.70 per common share with a term expiring June 30, 2026, alongside an additional 44 million warrants at the same exercise price and term, which will vest in tranches each time Prometic draws an additional amount of USD $10 million (CAD $12.5 million) under the Credit Facility. Drawing on the first 4 tranches of USD $10 million (CAD $12.5 million) would each cause 5 million warrants to vest, whereas the drawing on the second set of 4 tranches of USD $10 million (CDN $12.5 million) would each cause 6 million warrants to vest. The entering into of the Credit Facility is subject to Prometic obtaining TSX approval and finalizing the definitive documentation, which the parties expect to achieve on or about November 30, 2017.