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 Novartis reported additional analysis from the global Phase III SOLAR-1 trial investigating the alpha-specific PI3K inhibitor BYL719 (alpelisib) in combination with fulvestrant in men and postmenopausal women with PIK3CA mutated hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (Press release, Novartis, DEC 6, 2018, https://www.novartis.com/news/media-releases/novartis-investigational-byl719-alpelisib-plus-fulvestrant-consistently-improved-pfs-patients-pik3ca-mutated-hrher2-advanced-breast-cancer-new-solar-1-analyses [SID1234531929]).

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In SOLAR-1, the addition of BYL719 to fulvestrant nearly doubled median progression-free survival (PFS) in patients with PIK3CA mutated HR+/HER2- advanced breast cancer who progressed on or after an aromatase inhibitor (AI) compared to fulvestrant alone. In this analysis, BYL719 plus fulvestrant also showed consistent clinically meaningful treatment benefit after progression on an AI or after receiving up to one additional line of therapy for advanced breast cancer[1]. These data will be presented today during an oral presentation at the 2018 San Antonio Breast Cancer Symposium (SABCS) (Abstract #GS3-08).

Approximately 40% of patients living with HR+ advanced breast cancer have a PIK3CA mutation, which over activates the PI3K pathway[2]. When activated, the PI3K pathway is associated with tumor growth, resistance to endocrine treatment and a poor overall prognosis[3],[4]. Currently there are no approved treatments for breast cancer that specifically target this mutation.

"PIK3CA mutation is the most common actionable alteration in ER+ breast cancer, so it is encouraging to see a meaningfully prolonged PFS with BYL719 combination therapy in patients with PIK3CA mutated breast cancer who progressed on an aromatase inhibitor and who received up to one additional line of therapy prior to treatment with BYL719 plus fulvestrant," said Dejan Juric, MD, Director, Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center. "With the SOLAR-1 trial results, we can confidently say that identifying and targeting PIK3CA mutations is clinically important as we apply the precision oncology paradigm to breast cancer and continuously look for new treatment solutions to extend the lives of patients with this disease."

BYL719 in combination with fulvestrant consistently improved median PFS in patients with PIK3CA mutated HR+/HER2- advanced breast cancer who progressed within 12 months of AI treatment (mPFS: 11.0 months vs 6.8 months for fulvestrant alone) or received up to one additional line of therapy for advanced breast cancer (mPFS: 10.9 months vs 3.7 months, respectively).

Most adverse events were mild to moderate in severity and generally manageable through dose interruption, dose reductions and medical management. Treatment discontinuation rate due to adverse events in those with a PIK3CA mutation receiving BYL719 plus fulvestrant was 3% compared to 2% for fulvestrant alone. The most frequent all-grade adverse events (>=40%) were hyperglycemia (65% vs 9%), diarrhea (54% vs 11%), nausea (46% vs 20%) and rash (40% vs 6%). The most common grade 3/4 events (>=10%) were hyperglycemia (37% vs <1%) and rash (13% vs <1%)[1].

Mutation status of participants in SOLAR-1 was identified by a clinical trial assay developed by Qiagen*. A significant PFS benefit was observed for BYL719 plus fulvestrant in patients with a PIK3CA mutation regardless of whether the mutation was identified by a tumor tissue test or ctDNA test, suggesting the potential viability of using liquid biopsies to identify PIK3CA mutation status (tissue positive HR=0.65; mPFS 11.0 months; plasma positive HR=0.56; mPFS 10.9 months)[1].

Novartis has entered into agreements with both Qiagen and Foundation Medicine** to develop flexible companion diagnostic solutions for BYL719 that utilize both tumor tissue and plasma sample types.

"Our work to develop an effective PI3K inhibitor started more than two decades ago, and learning from multiple clinical trial experiences, we have been able to advance an investigational targeted therapy for patients with this specific breast cancer," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "SOLAR-1 is the first breast cancer trial to show potential utility of liquid biopsies. We are excited to collaborate with Qiagen and Foundation Medicine on tissue and plasma tests that, if approved, may help oncologists identify patients who could benefit from BYL719 plus fulvestrant."

The SOLAR-1 trial is ongoing to evaluate secondary endpoints, including overall survival and will be presented and discussed in the future. Overall survival (OS) results were immature at the time of data cut-off after 52% of events (HR=0.73; 95% CI 0.48-1.10; p=0.06; median not estimable vs 26.9 months). The prespecified O’Brien-Fleming stopping boundary was not crossed. Discussions with health authorities regarding the SOLAR-1 data have begun.

About SOLAR-1
SOLAR-1 is a global, Phase III randomized, double-blind, placebo-controlled trial studying investigational BYL719 in combination with fulvestrant for postmenopausal women with PIK3CA-mutated HR+/HER2- advanced or metastatic breast cancer that progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor[1].

The trial randomized 572 patients. Patients were allocated based on tumor tissue assessment to either a PIK3CA-mutated cohort or a PIK3CA non-mutated cohort. Within each cohort, patients were randomized in a 1:1 ratio to receive continuous oral treatment with BYL719 (300mg once daily) plus fulvestrant (500 mg every 28 days + Cycle 1 Day 15) or placebo plus fulvestrant. Stratification was based on visceral metastases and prior CDK4/6 inhibitor treatment[1].

The primary endpoint is local investigator assessed PFS using RECIST 1.1 for patients with a PIK3CA mutation. Secondary endpoints include but are not limited to overall survival, overall response rate, clinical benefit rate, health-related quality of life, efficacy in PIK3CA non-mutated cohort, safety and tolerability[1].

For the primary SOLAR-1 analysis, mutation status was determined by tumor tissue via polymerase chain reaction (PCR) analysis. Plasma ctDNA samples were also collected at baseline as a secondary endpoint. Plasma ctDNA mutation status of participants in SOLAR-1 was identified by an assay developed by Qiagen.

About BYL719 (alpelisib)
BYL719 is an investigational, orally bioavailable, alpha-specific PI3K inhibitor. In breast cancer cell lines harboring PIK3CA mutations, BYL719 has been shown to potentially inhibit the PI3K pathway and have antiproliferative effects. In addition, cancer cell lines with PIK3CA mutations were more sensitive to BYL719 than those without the mutation across a broad range of different cancers[5].