On December 6, 2019 Helix BioPharma Corp. (TSX, FSE: "HBP") ("Helix" or the "Company"), an immuno-oncology company developing innovative drug candidates for the prevention and treatment of cancer, reported it has closed a first tranche of a private placement financing for gross proceeds of CAD871,200. The Company expects to complete a second tranche of the private placement financing before the end of December.

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The terms of the placement are for the purchase of units at $1.20 per unit. Each unit is comprised of one common share and one common share purchase warrant. Each common share purchase warrant will entitle the holder to purchase one common share at an exercise price of $1.50 and have an expiry of five years from the date of issuance. Helix intends to use the net proceeds of the private placement for working capital and research and development activities.

ACM Alpha Consulting Management AG provided financial advisory services to Helix in connection with the private placement.

On December 6, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), reported that the United States Patent and Trademark Office has issued US patent 10,144,770, entitled "Chimeric Receptors and Uses Thereof in Immune Therapy." The ‘770 patent covers design and use of the chimeric Antibody-Coupled T-cell Receptor (ACTR) platform technology that enables an engineered immune cell to be targeted via an antibody to attack certain cell types, including cancer cells (Press release, Unum Therapeutics, DEC 6, 2018, View Source [SID1234531923]). An ACTR-expressing T cell offers a number of potential advantages over alternative cell therapy approaches and clinical proof-of-concept for the ACTR technology has been demonstrated in two independent clinical trials sponsored by Unum Therapeutics. ACTR therapeutic programs targeting non-Hodgkin lymphoma, multiple myeloma, and HER2+ advanced cancers are currently in early stages of clinical testing.

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The initial ACTR construct was developed by Dr. Dario Campana, a well-renowned cancer researcher recognized as an inventor of the chimeric antigen receptor that forms the basis for tisagenlecleucel, the world’s first approved CAR-T therapy. Working initially at St. Jude Children’s Research Hospital and later at the National University of Singapore, Dr. Campana and his team were able to demonstrate in mouse studies that ACTR-expressing T cells exhibit potent anti-tumor activity. Researchers at Unum Therapeutics extended upon this work, demonstrating that a wide range of functional ACTR receptors could be constructed using different building blocks derived from various human immune cell receptors.

Under the terms of a 2014 three-way license agreement between Unum Therapeutics, the National University of Singapore, and St. Jude Children’s Research Hospital, Unum Therapeutics controls exclusive, world-wide rights to develop and commercialize ACTR therapies covered by the ‘770 patent. Unum has continued to build a broad patent portfolio encompassing further enhancements to and novel applications of the ACTR technology. In addition to the ‘770 patent covering ACTR in the United States, previously granted patents protect the technology in Europe, Japan, and other important territories. The full text of the ‘770 patent is available from the US Patent and Trademark Office website at View Source;Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=10144770.PN.&OS=PN/10144770&RS=PN/10144770.

On December 6, 2018 GT Biopharma, Inc. (OTCQB: GTBP and Euronext Paris GTBP.PA) ("GT Biopharma" or the "Company"), an immuno-oncology biotechnology company focused on innovative treatments based on the Company’s proprietary NK-engager and Bispecific Antibody Drug Conjugate platforms, reported that it presented data demonstrating the effectiveness of the Company’s Tri-specific Killer Engagers (TriKEs) for the treatment of acute myeloid leukemia (AML) presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, GT Biopharma , DEC 6, 2018, View Source [SID1234539518]).

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Jeffrey Miller, MD, Deputy Director, Masonic Cancer Center, University of Minnesota commented, "These studies demonstrate the adaptability of the TriKE platform to optimize TriKE constructs and candidate selection in order to address unmet medical needs. We continue to work with our partners at GT Biopharma in moving the TriKE platform forward."

The Company’s TriKE product candidates are single-chain, tri-specific scFv recombinant fusion proteins composed of the variable regions of the heavy and light chains (or heavy chain only) of anti-CD16 antibodies, wild-type or a modified form of IL-15 and the variable regions of the heavy and light chains of an antibody designed to precisely target a specific tumor antigen. GT Biopharma utilizes the NK stimulating cytokine human IL-15 as a crosslinker between the two scFvs which is designed to provide a self-sustaining signal leading to the proliferation and activation of NK cells thus enhancing their ability to kill cancer cells mediated by antibody-dependent cell-mediated cytotoxicity (ADCC). GT Biopharma has an exclusive worldwide license agreement with the University of Minnesota to further develop and commercialize cancer therapies using proprietary TriKE technology developed by researchers at the university to target NK cells to cancer.

"We continue to be encouraged by the data from our Trike program being conducted by leading NK cell experts at the University of Minnesota. These findings have supported us with the confidence to proceed with our first-in-class TriKE, Phase 1 study," commented Raymond Urbanski, M.D., Ph.D., Chief Executive Officer of GT Biopharma. "We are grateful to renowned NK cell expert, Jeffrey Miller, MD, Deputy Director, Masonic Cancer Center, University of Minnesota and his team, and look forward to providing further updates as we continue to advance what we believe to be a potentially revolutionary product candidate."

Graduate student, Upasana Sunil Arvindam, MSc, BSc, working with Drs. Miller and Felices at the University of Minnesota, presented the abstract titled, "CD16-IL15-CLEC12A Tri-specific Killer Engager (TriKE) Drives NK Cell Expansion, Activation, and Antigen Specific Killing of Cancer Stem Cells in Acute Myeloid Leukemia," as part of the Acute Myeloid Leukemia: Novel Therapy, Excluding Transplantation: Poster I session at ASH (Free ASH Whitepaper). To access the presented poster, click here.

For the preclinical study, Dr. Arvindam and her team developed a 1615CLEC12A TriKE molecule to target AML cells using Natural Killer (NK) cells. This molecule contains an anti-CD16 camelid nanobody to activate NK cells, an anti-CLEC12A single chain variable fragment (scFv) to engage cancer targets, and an IL-15 molecule that drives NK cell priming, expansion and survival.

The CLEC12A TriKE was developed in a mammalian cell system to ensure that appropriate post-translational modifications are present. The researchers confirmed that the TriKE binds specifically to HL-60 and THP-1 target cells that express CLEC12A compared to Raji cells that do not express CLEC12A. Treatment of peripheral blood mononuclear cells (PBMCs) with the CLEC12A TriKE drives a significant increase in NK cell specific proliferation over 7 days as measured by Cell Trace dilution compared to treatment with a CLEC12A scFv or IL-15 alone (69.7 ± 6.7% vs 11.9 ± 2.5% vs 38.4 ± 7.3%). In these assays, the efficacy of the CLEC12A TriKE was comparable to the CD33 TriKE. The data demonstrates that the CLEC12A TriKE drives NK cell specific proliferation, degranulation, cytokine secretion, and killing of tumor targets in vitro. Apart from AML, CLEC12A is expressed on cancer cells and LSCs in patients with myelodysplastic syndromes (MDS).

The presented preclinical findings highlight the clinical potential of the CLEC12A TriKE individually or in combination with the CD33 TriKE for the treatment of MDS and AML and ultimately led to the establishment of a first-in-human Phase 1 study with GTB-3550 (OXS-3550), its first-in-class (TriKE), for the treatment of AML, MDS and mastocytosis, which GT Biopharma recently announced. The study will be led by Principal Investigator, Sarah A. Cooley, MD, MS, Associate Professor, Division of Hematology, Oncology and Transplantation at Masonic Cancer Center, University of Minnesota.

The abstract titled, "Induced Pluripotent Stem Cell-Derived NK Cells Genetically Modified to Express NKG2C/DAP12 Mediate Potent Function When Targeted through an NKG2C/IL-15/CD33 Tri-Specific Killer Engager (TriKE)," was presented in an oral presentation by graduate student Emily Chiu, PhD, Medical School, University of Minnesota. To access the presentation slides, click here.

Having demonstrated stable expression and intact signaling of NKG2C/DAP12 in iNK cells, Dr. Chiu and her team next created a TriKE molecule with single chain Fv fragments specific for NKG2C (on iNK cells) and CD33 (on AML cells), as well as IL15 (to support iNK cell survival and proliferation). Without the addition of NKG2C/CD33/IL15 TriKE, the frequencies of both NKG2C iNK cells and NKG2C/DAP12 iNK cells producing IFNg was relatively low (< 10%). Addition of NKG2C/IL15/CD33 TriKE in the assay markedly increased the frequency of IFNg production by both NKG2C iNK cells (19.1%) and NKG2C/DAP12 iNK cells (25.8%). Finally, the team directly tested the ability of the NKG2C/IL15/CD33 TriKE molecule to trigger target killing by engineered iNK cells monitored over a 24hour period. THP1 target cells were dye labeled and plated in wells with either NKG2C iNK cells or NKG2C/DAP12 iNK cells at a 5:1 effector-to-target ratio with or without NKG2C/CD33/IL15 TriKE. The researchers found that in the absence of TriKE, there was no killing of THP1 targets. In contrast, both NKG2C iNK cells and NKG2C/DAP12 iNK cells mediated robust THP1 killing with the addition of NKG2C/CD33/IL15 TriKE, with NKG2C/DAP12 iNK cells exhibiting the strongest response.

Results from the study provided a proof-of-concept that iNK cells engineered to express NKG2C/DAP12 can be used in combination with a novel NKG2C/IL15/CD33 TriKE molecule to effectively target cancer cells. Engaging NK cells through NKG2C, restricted to adaptive NK cells or genetically modified iPSC will be more specific than CD16, which will bind to CD16A on NK cells but also have off-target binding to CD16B on neutrophils. Because of the enormous expansion and engineering capacity of the iNK cell platform, the Company believes it is in a unique position to create an "off-the-shelf" NK cellular therapy that is targeted, specific and efficacious.

About Acute Myelogenous Leukemia (AML)

AML is the most common form of adult leukemia with 21,000 new cases expected in 2018 alone, according to the American Cancer Society. AML patients typically receive frontline therapy, most commonly chemotherapy, which includes cytarabine and an anthracycline, a therapy that has not changed in over 40 years. However, there remains a significant unmet need in these therapies with about half of AML patients experiencing relapses or requiring alternative therapies. The Company is developing GTB-3550 to serve as a relatively safe, cost-effective, and easy-to-use therapy for resistant/relapsing AML and could also be combined with chemotherapy as frontline therapy thus targeting the larger patient population

On December 6, 2018 Stemline Therapeutics, Inc. (Nasdaq: STML), a biopharmaceutical company focused on the development and potential commercialization of novel oncology therapeutics, reported that updated data from multiple ELZONRISTM (tagraxofusp; SL-401) clinical trials at the 2018 ASH (Free ASH Whitepaper) Annual Meeting (Press release, Stemline Therapeutics, DEC 6, 2018, View Source [SID1234531924]). Presentations are now available on the Stemline website, www.stemline.com, under the Scientific Presentations tab.

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Key Outcomes from Pivotal Trial of ELZONRIS in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Across all 3 stages, 42 patients received ELZONRIS (12 ug/kg/day)
• In first-line patients with BPDCN, ELZONRIS (12 ug/kg/day)
– 90% (26/29) overall response rate (ORR)
– 72% (21/29) rate of CR + CRc (complete response + clinical CR [CR with residual skin abnormality])
– 45% (13/29) of patients were bridged to stem cell transplant (SCT)
• In relapsed/refractory patients with BPDCN, ELZONRIS (12 ug/kg/day)
– 69% (9/13) ORR
– 38% (5/13) CR + CRc + CRi rate
– 1 patient was bridged to SCT
• Median overall survival (OS) was not yet reached in first-line patients treated with ELZONRIS at 12 ug/kg/day across all stages. Median follow up time is 23.0 months (range of 0.2 – 41+ months)
• Most common treatment-related adverse events (TRAEs) in all patients treated across all trials at 12 ug/kg/day dose (N=148) were: alanine aminotransferase increase (43.9%), aspartate aminotransferase increase (43.9%), hypoalbuminemia (43.9%), and thrombocytopenia (26.4%). TRAEs included capillary leak syndrome (CLS) (16.9%) which was grade 5 in 1.5% (3/202) of patients across all trials and doses and 0.6% (1/166) of patients across all trials at 12 ug/kg/day; a myocardial infarction, grade 5, occurred in a patient (12 ug/kg/day) with grade 4 CLS, as previously reported.

Stage 3 pivotal cohort (13 first-line BPDCN patients treated with SL-401 at 12 ug/kg/day):
• Met its primary endpoint with a 54% (7/13) CR + CRc rate (95% CI: 25.1, 80.8)
• 77% (10/13) ORR
• 46% (6/13) of patients were bridged to SCT
In the U.S., the ELZONRIS biologics license application (BLA) is under Priority Review, with a February 21, 2019 PDUFA action date

In the E.U., the European Medicines Agency (EMA) has granted accelerated assessment to the planned Marketing Authorization Application (MAA), which is expected to be submitted in the first quarter of 2019
Key Outcomes from Ongoing Clinical Trial of ELZONRIS in Patients with Relapsed/Refractory Chronic Myelomonocytic Leukemia (CMML)

ELZONRIS demonstrated efficacy (spleen and bone marrow responses), with a manageable safety profile, in patients with relapsed/refractory CMML, an area of unmet medical need

100% of evaluable patients had reduction in baseline splenomegaly
– 80% had reduction by ≥50%
– 67% with baseline spleen size ≥5cm had reduction by ≥50%

3 bone marrow complete responses (BMCRs)

1 patient bridged to stem cell transplant in remission on ELZONRIS

Most common TRAEs include hypoalbuminemia (35%), thrombocytopenia (35%), nausea (30%) and vomiting (30%). Most common TRAEs, grade 3+, include thrombocytopenia (35%) and nausea (5%). CLS was reported in 15% of patients, with no cases of grade 3 or higher observed

Splenomegaly has historically been associated with serious sequelae including early satiety and intractable pain, as well as poor transplant outcomes and a higher propensity for AML transformation

Targeting the proliferative component of CMML, namely alleviation of splenomegaly, could result in meaningful clinical benefit and address a key unmet medical need
Next Steps

Patient enrollment and follow up continues, and additional updates are planned in 2019

Based on the encouraging results seen in this trial, a registrational trial design, or pivotal cohort, is being designed
Key Outcomes from Ongoing Trial of ELZONRIS in Patients with Relapsed/Refractory Myelofibrosis

ELZONRIS monotherapy demonstrated efficacy (improvements in splenomegaly), with a manageable safety profile, in patients with relapsed/refractory MF, an area of unmet medical need; Patient enrollment and follow up continues

100% of evaluable patients with monocytosis and baseline spleen size ≥5cm, had reduction in baseline splenomegaly
– 80% had reduction by ≥29%; 40% had reduction by ≥45%
– Historically, monocytosis has been associated with poor prognosis in certain MF patients

57% of evaluable patients, with baseline spleen size ≥5cm, had reduction in baseline splenomegaly
– 43% had reduction by ≥29%; 21% had reduction by ≥45%

6 patients with spleen response had treatment duration of 6+ months; 5 patients ongoing
– 5 patients with baseline thrombocytopenia (platelet count <100K) had treatment duration of 6+ months; 4 ongoing
– 3 patients with baseline monocytosis (>1×109/L) had treatment duration of 8+ months; 2 patients ongoing

Initial quality of life (QOL) assessments appear promising; full symptom score analyses are ongoing

Most common TRAEs include headache and hypoalbuminemia (each 22%), and alanine aminotransferase increased and thrombocytopenia (each 17%). The most common TRAE, grade 3+, was thrombocytopenia (8%). There was one case of CLS, which was grade 3.
Next Steps

Patient enrollment and follow up continues, and additional updates are planned in 2019

Based on these encouraging results, next steps are being evaluated including single agent, combination, and registration-directed trials in patients with relapsed/refractory MF, including in poor-prognosis MF patients with monocytosis, an area of unmet medical need
Ivan Bergstein, M.D., CEO of Stemline, commented "The ELZONRIS clinical presentations showcased at ASH (Free ASH Whitepaper) demonstrate a broad clinical potential in a wide range of malignancies. In particular, we believe that our data in relapsed/refractory CMML and MF provides important clinical proof-of-concept in two indications with unmet medical need, and underscores just two of the many potential expansion opportunities that targeting CD123 offers. At ASH (Free ASH Whitepaper), we continued to ramp-up our disease awareness campaign for BPDCN ahead of the upcoming FDA decision on the ELZONRIS BLA. Also, our sales force is prepared and poised to launch ELZONRIS, should approval be obtained. In parallel, our clinical development team is moving forward with plans to expand efforts, including initiating one or more registration-directed trials in indications beyond BPDN, while also continuing to pursue novel entry points in CD123+ acute myeloid leukemia (AML) and other malignancies."

About BPDCN
To learn more about BPDCN, please visit the disease awareness website at www.bpdcninfo.com.

On December 6, 2018 RedHill Biopharma Ltd. (Nasdaq:RDHL) (Tel-Aviv Stock Exchange:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on proprietary drugs for gastrointestinal diseases, reported the pricing of its previously reported underwritten public offering for a total number of 2,857,143 American Depositary Shares ("ADSs"), each representing ten of its ordinary shares, at a public offering price of $7.00 per ADS (Press release, RedHill Biopharma, DEC 6, 2018, View Source [SID1234531941]).

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Gross proceeds from the sale of the ADSs before underwriting discounts and commissions and other offering expenses are expected to be approximately $20 million. The offering is expected to close on or about December 11, 2018, subject to customary closing conditions. The Company has also granted the underwriters a 30-day option to purchase up to an additional 15% of the number of ADSs offered to the public at the public offering price, less underwriting discount.

Ladenburg Thalmann & Co. Inc., a subsidiary of Ladenburg Thalmann Financial Services Inc. (NYSE American: LTS) and Nomura Securities International, Inc. are acting as joint book-running managers. H.C. Wainwright & Co., LLC is acting as lead manager and LifeSci Capital LLC, Ascendiant Capital Markets, LLC, SMBC Nikko Securities America, Inc. and WBB Securities LLC are acting as co-managers for the offering. Roth Capital Partners is acting as financial advisor to the Company in connection with the offering.

The Company intends to use the net proceeds from the offering, together with its existing cash and cash equivalents, to fund preparations for TALICIA (H. pylori) commercial launch and commercialization activities, clinical development programs, including initiation of a pivotal Phase 3 study with RHB-204 for NTM, preparations for a second Phase 3 study with RHB-104 for Crohn’s disease and for acquisitions and general corporate purposes.

The ADSs described above will be issued pursuant to shelf registration statements that were previously filed with the Securities and Exchange Commission (the "SEC") and declared effective by the SEC on March 11, 2016 and July 31, 2018, respectively. A preliminary prospectus supplement and accompanying prospectus related to the offering has been filed with the SEC and is available on the SEC’s website located at www.sec.gov. Before you invest, you should read the preliminary prospectus supplement and accompanying prospectus and other documents we have filed with the SEC for more complete information about us and this offering. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering may be obtained by contacting Ladenburg Thalmann & Co. Inc., Prospectus Department, 277 Park Avenue, 26th Floor, New York, New York 10172, by calling (212) 409-2000, or by email at [email protected]; or Nomura Securities International, Inc., Attention: Equity Syndicate Department, Worldwide Plaza, 309 West 49th Street, New York, NY 10019-7316, or by telephone at 212-667-9000, or by email at [email protected].

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