On November 12, 2018 UroGen Pharma Ltd. (Nasdaq:URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in the field of urology, with a focus on uro-oncology, reported financial results for third quarter ended September 30, 2018 and that it has completed enrollment of the UGN-101 OLYMPUS Phase 3 Trial in patients with low-grade upper tract urothelial cancer (LG UTUC) following a recent pre-New Drug Application (NDA) meeting held with the U.S. Food and Drug Administration (FDA) (Press release, UroGen Pharma, NOV 12, 2018, View Source [SID1234531211]).

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At the pre-NDA meeting, the company presented updated data from this open-label, single arm Phase 3 study. The meeting resulted in agreement on the required information for the NDA submission and suitability for NDA submission of primary endpoint (Complete Response) data for the approximately 65 patients enrolled to date.

UroGen plans to present the topline data in January 2019, with the full dataset expected at a medical meeting in the second quarter of 2019.

"We are pleased by the FDA’s support for UGN-101 and recognition of the potential clinical benefit that UGN-101 presents for LG UTUC as a potentially organ-sparing, non-invasive therapy for this disease," said Ron Bentsur, Chief Executive Officer of UroGen. "We are excited about the progress that we continue to make across our clinical pipeline and look forward to collaborating with the FDA to bring this potentially transformative therapy to patients with LG UTUC."

Breakthrough Therapy Designation (BTD) was granted by the FDA for UGN1-101 for the treatment of LG UTUC in October 2018. UroGen remains on track to initiate the UGN-101 Rolling NDA Submission to the FDA in Q4 2018 and complete the submission in Q2 2019, with potential approval expected in 2019.

Additional Highlights and Upcoming Milestones

UGN-102 Clinical Development:
UroGen is enrolling patients as part of its Phase 2b single-arm, open-label, multi-center trial designed to assess the efficacy and safety of UGN-102 (mitomycin gel) for intravesical instillation as a potential first-line chemoablation agent in the treatment of patients with LG Non-Muscle Invasive Bladder Cancer (NMIBC) at risk for recurrence.
Initial data from the trial is expected in 1H 2019.
Similar to LG UTUC, there are currently no drugs approved by the FDA as first-line treatment for NMIBC, and only three drugs have been approved by the FDA, all as adjuvant treatments, following TURBT (transurethral resection of bladder tumor).
UGN-102 represents a very substantial opportunity in UroGen’s pipeline with the potential to initially address up to approximately 85,000 patients for whom TURBT is no longer effective.1
Advancing the Potential of the RTGel Platform:
Allergan continues to enroll patients in its Phase 2 trial of BotuGel, UroGen’s RTGel in combination with BOTOX2, for the treatment of overactive bladder. This clinical trial, if successful, has the potential to demonstrate the broad applicability of the RTGel platform beyond uro-oncology. Phase 2 data is expected in 2019.
Corporate Developments:
UroGen strengthened its leadership team with the appointment of Jones "Woody" Bryan, Ph.D., as Senior Vice President, Business Development. Dr. Bryan is a seasoned industry veteran who brings over 25 years of industry experience. He is focused on the integration of corporate strategy and business development to assess potential partnerships, both inbound and outbound, and bolster UroGen’s product portfolio.
Third Quarter 2018 Financial Results

As of September 30, 2018, cash and cash equivalents totaled $109.5 million.
Research and development expenses for the nine months ended September 30, 2018 were $25.5 million, including non-cash share-based compensation expense of $9.1 million. Research and development expenses for the three months ended September 30, 2018 were $9.6 million, including non-cash share-based compensation expense of $3.8 million.
General and administrative expenses for the nine months ended September 30, 2018 were $27.0 million, including non-cash share-based compensation expense of $12.7 million. General and administrative expenses for the three months ended September 30, 2018 were $10.7 million, including non-cash share-based compensation expense of $5.7 million.
The Company reported a net loss of $51.9 million, or basic and diluted net loss per ordinary share of $3.30, for the nine months ended September 30, 2018. The Company reported a net loss of $20.5 million, or basic and diluted net loss per ordinary share of $1.28, for the three months ended September 30, 2018.
Conference Call & Webcast Information

Members of UroGen’s management team will host a live conference call and webcast today at 8:30 a.m. Eastern Time to review the Company’s financial results and provide a general business update. Due to observance of the Veteran’s Day holiday in the United States on November 12, 2018, UroGen’s corresponding 6-K will be filed with the Securities and Exchange Commission (SEC) before market on November 13, 2018.

The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call (888) 771-4371 (U.S.) or (847) 585-4405 (International) to listen to the live conference call. The conference ID number for the live call will be 47697839. An archive of the webcast will be available for two weeks on the Company’s website.

On November 12, 2018 Bicycle Therapeutics, a biotechnology company pioneering a new class of therapeutics based on its proprietary bicyclic peptide (Bicycles) product platform, reported that its scientific co-founder, Sir Gregory Winter, the 2018 winner of the Nobel Prize in chemistry, will deliver the plenary keynote at the 2018 Protein and Antibody Engineering (PEGS) Summit Europe, held in Lisbon, Portugal (Press release, Bicycle Therapeutics, NOV 12, 2018, View Source [SID1234531210]). The title of his address, which will be delivered today at 4:20 p.m. GMT, is "Bicycles and Bicycle Drug Conjugates."

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In addition, Bicycle will present a poster highlighting preclinical research that supports the development of CD137 Bicycle agonists as novel cancer immunotherapies. The poster, which has been selected as a highlighted oral presentation, is titled "Novel Multimers of Bicyclic Peptides Cluster and Activate CD137 (4-1BB): A Costimulatory T-Cell Checkpoint Receptor" and will be presented on Thursday, Nov. 15 at 3:20 p.m. GMT.

On November 12, 2018 Medigene AG (FSE: MDG1, Prime Standard, SDAX) reported that it has entered into an exclusive license agreement with Leiden University Medical Center (LUMC), the Netherlands, for worldwide rights to develop, manufacture, and commercialize an HA-1-specific T cell receptor (TCR) as a targeted immunotherapy for cancer (Press release, MediGene, NOV 12, 2018, View Source [SID1234531209]).

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The TCR specific for the minor histocompatibility antigen HA-1 was developed by LUMC and tested for preliminary safety and tolerability in a Phase I clinical trial involving five patients. HA-1 is a well-characterized antigen expressed in cells of the hematopoietic system, in leukemia and lymphoma cells, as well as expressed in various solid tumors.

Dr Kai Pinkernell, CMO and CDO of Medigene , said: "We are excited to have licensed this HA-1-targeting T cell receptor, which has already undergone early clinical testing, to complement Medigene’s preclinical and clinical development program. Scientists from LUMC and Medigene have had a longstanding shared scientific interest and exchange on HA-1 and we look forward to our future interactions. Our own extensive research and development for the HA-1 antigen confirms the potential of this approach in general and this TCR candidate in particular. Its potential applicability in both liquid and solid tumors makes strategic sense within our growing internal pipeline."

Mirjam H.M. Heemskerk, PhD, Associate Professor of the Department of Hematology at the Leiden University Medical Center , said: "Medigene is an ideal partner to further advance this promising TCR candidate given their deep scientific expertise, broad development work and strong focus on TCRs. We share a common vision of developing T cell receptor therapies to offer seriously ill cancer patients much-needed treatment alternatives."

Under the terms of the agreement, Medigene will receive the exclusive worldwide development and commercialization rights to the HA-1-specific TCR developed by LUMC. In return, LUMC will receive a one-time payment along with certain milestone payments. Upon commercialization, LUMC is eligible for royalties in the low-single digit percentage range. Confidentiality was agreed regarding further financial details.

Terms of the deal do not materially impact Medigene’s financial guidance for the balance of the year 2018.

About HA-1: The HA-1 antigen has been extensively studied by Medigene’s research team. It is a clinically validated T cell target used in stem cell transplantation (SCT). HA-1, as a single nucleotide polymorphism (SNP), is easily detected by a PCR method and shows a well-characterized tissue expression pattern.

On November 12, 2018 AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical-stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, reported that it will present at the Jefferies 2018 London Healthcare Conference in London, UK, taking place November 14 to 15, 2018 (Press release, AC Immune, NOV 12, 2018, View Source;jsessionid=I3EHPF-DGpWZMr3XX77giholoUVnI9bmt9_kIt_mqlDRUYKezPeM!702079892 [SID1234531208]).

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Jefferies 2018 London Healthcare Conference
Date: November 15, 2018 | 12:40 pm GMT
Presenter: Prof. Andrea Pfeifer, CEO, AC Immune

A webcast of the presentation will be available on the Investor Page of AC Immune’s investor page and at the Jefferies 2018 Healthcare Conference website and will be active for 90 days following the event.

On November 12, 2018 AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) reported that the US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) for Priority Review for the use of Lynparza (olaparib) tablets as a maintenance treatment in patients with newly-diagnosed, BRCA-mutated (BRCAm) advanced ovarian cancer who were in complete or partial response following 1st-line standard platinum-based chemotherapy (Press release, AstraZeneca, NOV 12, 2018, View Source [SID1234531207]). A Prescription Drug User Fee Act (PDUFA) date is set for the first quarter of 2019.

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This is the first US regulatory submission acceptance for a poly ADP-ribose polymerase (PARP) inhibitor in the 1st-line maintenance setting for advanced ovarian cancer, and if approved will be the fourth indication for Lynparza in the US.

This submission was based on positive results from the pivotal Phase III SOLO-1 trial. The trial showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) for Lynparza compared to placebo, reducing the risk of disease progression or death by 70% in patients with newly-diagnosed, BRCAm advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy (HR 0.30 [95% CI 0.23-0.41], p<0.001). Of those receiving Lynparza, 60% remained progression-free at 36 months compared to 27% of women in the placebo arm. These data were recently presented for the first time at the ESMO (Free ESMO Whitepaper) 2018 Congress (European Society for Medical Oncology) and published online in the New England Journal of Medicine.

Lynparza is currently approved in over 60 countries for the treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status. It is also approved in several countries, including the US and Japan, for germline BRCAm HER2-negative metastatic breast cancer – regulatory reviews are underway in the EU, Japan and other markets.

About SOLO-1

SOLO-1 is a Phase III randomised, double-blinded, placebo-controlled, multicentre trial to evaluate the efficacy and safety of Lynparza tablets (300mg twice daily) as maintenance monotherapy compared with placebo, in newly-diagnosed patients with BRCAm advanced ovarian cancer following platinum-based chemotherapy. The trial randomised 391 patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy. Patients were randomised (2:1) to receive Lynparza or placebo for up to two years or until disease progression (at the investigator’s discretion). The primary endpoint was PFS and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival.

About Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-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 being tested in a range of DDR-deficient tumour types.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

About ovarian cancer

Ovarian cancer is a leading cause of cancer death in women worldwide, with a five-year survival rate of 19%.[i] In 2018, there were over 295,000 new cases diagnosed and around 185,000 deaths.[ii] For newly-diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission or cure.[iii],[iv],[v],[vi]

About BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in 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, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.