On December 6, 2018 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of oncology drug candidates, all of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported it has filed a request with the U.S. Food and Drug Administration ("FDA") for Orphan Drug Status for its drug candidate WP1066 (Press release, Moleculin, DEC 6, 2018, View Source [SID1234531927]).

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"Clinical progress with WP1066 has been encouraging," commented Walter Klemp, Moleculin’s Chairman and CEO. "Given its potential to address rare and difficult to treat cancers, including glioblastoma, we believe WP1066 is well positioned to qualify for Orphan Drug Status."

The FDA grants orphan drug designation to drugs and biologics that are intended for the treatment of rare diseases that affect fewer than 200,000 people in the U.S. Orphan drug status is intended to facilitate drug development for rare diseases and may provide several benefits to drug developers, including tax credits for qualified clinical trials costs, exemptions from certain FDA application fees, and seven years of market exclusivity upon regulatory product approval.

On December 6, 2018 Xspray Pharma AB (publ) ("Xspray" or the "Company") reported the company has successfully carried out a directed share issue at a subscription price of SEK 67 per share (Press release, Xspray, DEC 6, 2018, View Source [SID1234650105]). The subscription price corresponds to a discount of approximately 3 percent compared with today’s VWAP, 6 December 2018. The subscription price has been determined through an accelerated book-building procedure.

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A group of Swedish and international institutional investors, among others Unionen, Third Swedish National Pension Fund and Forth Swedish National Pension Fund, have subscribed for shares in the directed share issue. The Company believes that the flexibility of a placing without pre-emption right for existing shareholders is the most appropriate way to diversify the shareholder base among institutional investors prior to the planned list change of the Company’s share to Nasdaq Stockholm’s main list during 2019, and at the same time raise capital in a time efficient manner.

Following the positive data announced on 10 October 2018 for the Company’s lead product, HyNap-Dasa, the Company intends to use the proceeds from the directed share issue to i) continue development of its product portfolio; ii) develop its product candidates through registration; and iii) accelerate the development of product candidate HyNap-Nilo in order to be ready to launch the product earlier than previously planned.

Per Andersson, CEO, Xspray Pharma, comments:

"As a result of the positive results for the product candidate HyNap-Dasa, presented earlier this fall, we are in a strong position to bring our unique HyNap compositions, comprising a number of protein kinase inhibitors (PKIs), to the market. This is an important step towards becoming a powerhouse for PKIs where we address relevant medical needs and more accessible pharmaceuticals to the cancer market."

The directed share issue is expected to raise proceeds for the Company of approximately SEK 92 million before transaction costs. The subscription price has been determined through an accelerated book-building procedure. The directed share issue will result in an increase of the number of shares in Xspray of 1,370,000, from 13,706,460 to 15,076,460, and an increase in the share capital by SEK 1,370,000, from SEK 13,706,460 to SEK 15,076,460, resulting in a dilution of approximately 9.1 percent.

In connection with the directed share issue, the Company has, with customary exceptions, agreed to a lock-up undertaking on future share issuances for a period of 90 days after the directed share issue. In addition, the management and board of directors have undertaken not to sell any shares in Xspray during the same period, subject to customary exceptions.

Advisers

In conjunction with the capital raising, the Company has engaged Carnegie Investment Bank as bookrunner and adviser, Zonda Partners as adviser and Vinge as legal adviser.

On December 6, 2018 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported additional data on patterns of clinical relapses (including organ or site of recurrence), as well as results from a preplanned secondary efficacy analysis across various predefined subgroups from the prospective, randomized, single-blinded, controlled Phase 2b independent investigator-sponsored clinical trial of the combination of trastuzumab (Herceptin) +/- nelipepimut-S (NeuVax, NPS) targeting HER2 low-expressing breast cancer patient cohorts at the 41st San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX (Press release, Sellas Life Sciences, DEC 6, 2018, View Source [SID1234531928]).

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These new data show a decrease in the total number of clinically detectable relapses with the combination of NPS + trastuzumab (7.5%) vs. trastuzumab alone (27.3%), p-value 0.004, which represents a 72.5% relative reduction in risk of relapse across time with a median follow up of 26.1 months in favor of the combination arm. Results from a planned analysis (log-rank) of the difference in disease free survival (DFS) outcomes between the two arms of the study in prespecified TNBC patient subgroups (patients who received neoadjuvant chemotherapy, expressed lower HER2, were 51 years or older, or had AJCC 7th Edition stage I/II TNBC), showed a clinically meaningful and statistically significant effect (p-value range: 0.004 – 0.014) in these subgroups in favor of the NPS plus trastuzumab combination arm. There was an average decrease of 84.2% in the relative risk of relapse or death at 24 months across these four subgroups of TNBC patients treated with NPS plus trastuzumab vs trastuzumab alone. The full data are summarized in the table below:

Comparison between NPS + trastuzumab vs. trastuzumab arms
Patient subgroups within the TNBC cohort Hazard Ratio (HR) HR 95% Confidence Interval P-value
(difference in favor of NPS + trastuzumab) Decrease in relative risk of relapse or death at 24 mos. (in favor of NPS + trastuzumab)
Received Neoadjuvant Chemotherapy 0.226 0.063 – 0.815 0.013 78.1%
Harbored BC with HER2 IHC 1+ expression level 0.178 0.038 – 0.837 0.014 81.3%
Aged ≥ 51 years 0.144 0.031 – 0.656 0.004 77.4%
AJCC 7 Stage I/II at diagnosis Incalculable* N/A 0.006 100%
*no DFS events occurred in AJCC 7 stage I/II TNBC patients treated with NPS plus trastuzumab.

"These new data provide insights on the pattern of clinically detectable relapses across various sites/organs, as well as add to our knowledge of the specific potential benefit distribution within the TNBC cohort. The results in four predefined TNBC subgroups inform us of the types of TNBC patients with residual disease after neoadjuvant chemotherapy who may potentially benefit when treated with NPS plus trastuzumab in the adjuvant setting. As previously announced, we are on track to meet with the U.S. Food and Drug Administration this month on the most expeditious and appropriate development path for NPS in TNBC," said Nicholas J. Sarlis, MD, PhD, Executive Vice President and Chief Medical Officer of SELLAS.

"We are very pleased with the results of these new analyses which indicate that the NPS plus trastuzumab combination – when given in the adjuvant setting after frontline therapy – could potentially improve outcomes across specific predefined subgroups of patients with early-stage TNBC, an aggressive subtype of breast cancer. The clinically meaningful and statistically significant decrease in the frequency of clinically detectable relapses – with a median follow-up of over 26 months – indicates a high degree of internal consistency," commented Elizabeth A. Mittendorf, MD, PhD, Rob and Karen Hale Distinguished Chair in Surgical Oncology, Director of Research, Breast Surgical Oncology Brigham and Women’s Hospital, Director, Breast Immuno-Oncology Program Dana-Farber/Brigham and Women’s Cancer Center, and the Principal Investigator of the Phase 2b study. "The data presented today are consistent with the previously reported beneficial effect seen in the TNBC cohort at large and are consistent with the immunobiological mechanism of action of nelipepimut-S."

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

SABCS Presentation Information

Date and Time: Thursday, December 6, 2018; 8:00 – 10:00 am ET
Poster Session 2: Treatment: Immunotherapy (clinical)
Poster Hall Location: Hall 1
Abstract ID: P2-09-01
Title: Subgroups analysis of a multicenter, prospective, randomized, blinded phase 2b trial of trastuzumab + nelipeptimut-S (NeuVax) vs. trastuzumab for prevention of recurrence in breast cancer patients

About SABCS

The mission of the SABC Symposium (SABCS) is to provide state-of-the-art information on breast cancer research. Since 2007, the SABCS has been jointly sponsored by the Cancer Therapy & Research Center (CTRC) at the University of Texas Health Science Center – San Antonio, the Baylor College of Medicine and the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

On December 6, 2018 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported an expansion of its existing cell therapy collaboration with Novartis, to include the ex vivo development of innovative cell therapies using certain ocular stem cells (Press release, Intellia Therapeutics, DEC 6, 2018, View Source [SID1234531945]). As part of the updated collaboration terms, Novartis will have the right to develop CRISPR/Cas9-based products for one or more targets using these stem cells. Intellia will receive a one-time $10 million cash payment and, consistent with the original collaboration agreement, Intellia also is eligible to receive downstream success-based milestones and royalties.

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With the collaboration expansion announced today, Intellia will gain expanded rights to Novartis’ lipid nanoparticle (LNP) technology for all genome editing applications in both in vivo and ex vivo settings. This licensed LNP technology is the foundation of Intellia’s proprietary modular delivery system of CRISPR/Cas9 for its in vivo product pipeline. Intellia retains rights to all other in vivo and ex vivo applications of CRISPR/Cas9, including for eye disorders, subject to certain in vivo target selection options by Novartis set forth in the original agreement.

"Genome editing enhancements made by CRISPR/Cas9 will enable the next generation of cell therapies. With our collaborator, Novartis, we are broadening the ex vivo application of our CRISPR/Cas9 technology from hematopoietic stem cells, or HSCs, to ocular stem cells. We are pleased to expand our relationship with Novartis, and to continue to work together to develop cell therapies," said Intellia President and Chief Executive Officer John Leonard, M.D. "Broader rights to Novartis’ LNP technology will assist our efforts to apply this technology in ex vivo settings for the development of proprietary cell therapies, just as we have done to develop our proprietary modular delivery system for in vivo products in the liver and other organs."

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