On April 24, 2018 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported results from the QUADRA study, which was designed to assess clinical benefit of ZEJULA treatment in heavily pre-treated patients with ovarian cancer (Press release, TESARO, APR 24, 2018, View Source [SID1234525646]). Results successfully achieved the pre-specified primary endpoint and demonstrated ZEJULA monotherapy activity in a biomarker selected patient population.

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Previous studies have shown PARP inhibitor activity in the late-line treatment of patients with BRCA mutations. QUADRA, a single arm study (n=461), was conducted to assess the activity of ZEJULA monotherapy in the fourth-line plus treatment of specific ovarian cancer patient populations. Of the 92% of QUADRA participants who were PARP inhibitor naïve, 15% had a BRCA mutation, over two-thirds were platinum resistant/refractory and 63% had received prior bevacizumab.

ZEJULA demonstrated activity in the primary efficacy population of fourth and fifth-line HRD positive patients who were PARP inhibitor naïve, and platinum sensitive (n=45), with an objective response rate (ORR) of 29%, and duration of response (DOR) of 9.2 months. In patients who were fourth line or greater with BRCA mutations, including platinum-sensitive, resistant and refractory, (n=55), the ORR was 31% and the median DOR was 9.4 months.

At a starting dose of 300 milligrams of ZEJULA, the most commonly observed adverse events were consistent with prior clinical experience and included myelosuppression, which was generally managed via dose modifications. TESARO intends to discuss a biomarker focused regulatory submission with the U.S. Food and Drug Administration (FDA) for a potential supplemental New Drug Application (sNDA) in the second half of 2018.

"These results demonstrated that ZEJULA is active as a late-line treatment for patients beyond those with BRCA mutations, which is the only treatment setting in which PARP inhibitors are approved today. In addition, the QUADRA data describe ZEJULA monotherapy activity in platinum-resistant/refractory patients, providing important context for our TOPACIO study of ZEJULA in combination with an anti-PD-1 inhibitor," said Mary Lynne Hedley, President and COO of TESARO. "With QUADRA data in hand, we continue to advance our mission to provide all patients with ovarian cancer an opportunity to benefit from treatment with ZEJULA, and we are extremely grateful to the patients, caregivers, and investigators who took part in this study."

Beyond QUADRA, clinical trials of niraparib in ovarian cancer include:

First Line:

PRIMA: Monotherapy Phase 3 trial for patients with first-line ovarian cancer regardless of biomarker status expected to complete enrollment in Q2 2018; data anticipated in 2019
OVARIO: Combination Phase 2 trial assessing ZEJULA with bevacizumab for patients with newly diagnosed ovarian cancer
FIRST: Combination Phase 3 clinical trial of chemotherapy ± TSR-042, and ZEJULA in first-line ovarian cancer to be initiated in 1H 2018
Recurrent:

NOVA: Monotherapy Phase 3 trial for patients with platinum sensitive, recurrent ovarian cancer, regardless of biomarker status (complete; patients being followed for overall survival)
AVANOVA: Combination Phase 2 trial with bevacizumab for patients with recurrent ovarian cancer; anticipate data to be available in 2H 2018 to support data submission for a meeting held in 2019
Platinum-Resistant:

TOPACIO: Combination Phase 2 trial with anti-PD-1 for patients with platinum-resistant ovarian cancer or triple negative breast cancer (abstracts accepted for presentation at ASCO (Free ASCO Whitepaper))
Product Lifecycle:

A tablet formulation of ZEJULA is in development.
About the QUADRA Clinical Trial
QUADRA is an open-label, single arm trial designed to evaluate the safety and efficacy of ZEJULA in the treatment setting of ovarian cancer. Patients were enrolled and received a starting dose of 300 milligrams of niraparib once per day. The primary endpoint of this study was objective response rate (ORR) per RECIST in the fourth and fifth-line HRD positive patients who were PARP inhibitor naïve, and platinum sensitive. Other endpoints include durability of response, disease control rate, progression free survival (PFS), overall survival (OS) and safety and tolerability.

About ZEJULA (Niraparib)
Niraparib is marketed in the United States and Europe under trade name ZEJULA. ZEJULA (niraparib) is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

ZEJULA (niraparib) Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in some clinical studies. Discontinue ZEJULA if MDS/AML is confirmed. Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time.

Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.

On April 24, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported high-level results from the Phase III ARCTIC trial in patients with locally-advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least two prior treatments (Press release, AstraZeneca, APR 24, 2018, View Source [SID1234525609]). This randomised, open-label, multi-centre trial assessed the efficacy and safety of the combination of Imfinzi (durvalumab) plus tremelimumab, as well as Imfinzi and tremelimumab monotherapies, versus standard-of-care chemotherapy (SoC) in patients with PDL1-low/negative NSCLC (sub-study B), and Imfinzi monotherapy versus SoC in patients with PDL1-high NSCLC (sub-study A).

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In sub-study B, the combination of Imfinzi plus tremelimumab in patients with PD-L1 low/negative NSCLC did not meet the primary endpoints of a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) and overall survival (OS) compared to SoC. Activity and safety of monotherapy arms of sub-study B were consistent with prior published data.

Sub-study A was not powered for statistical significance; however, Imfinzi monotherapy showed a clinically-meaningful reduction in the risk of death compared to chemotherapy.

Full data from the ARCTIC trial will be presented at a forthcoming medical meeting.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "While we are disappointed that the combination of Imfinzi plus tremelimumab did not result in a statistically-significant survival benefit in this heavily pre-treated patient population, we are encouraged by the activity of Imfinzi monotherapy observed in this trial and look forward to presenting the full data from the ARCTIC trial at an upcoming medical meeting."

AstraZeneca recently received approval from the US FDA for Imfinzi for the treatment of patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

NOTES TO EDITORS
About ARCTIC

The ARCTIC trial was a randomised, open-label, multi-centre, global Phase III trial containing two sub-studies: sub-study A (1:1 randomisation of patients with PDL1-high tumours to Imfinzi (durvalumab) vs. SoC) and sub-study B (2:3:1:2 randomisation of patients with PDL1-low/negative tumours to Imfinzi monotherapy, Imfinzi plus tremelimumab or tremelimumab vs SoC). Tumour PD-L1 expression was assessed with the Ventana PD-L1 (SP263) assay with PD-L1 high defined as ≥25% of tumour cells with membrane staining.

About Imfinzi

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In February 2018, Imfinzi received US FDA approval for the treatment of patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. Imfinzi also received accelerated approval in the US for the treatment of patients with locally-advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA-4 monoclonal antibody and potential new medicine, as a first-line treatment for patients with NSCLC, small cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.

About tremelimumab

Tremelimumab is a human monoclonal antibody and potential new medicines that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. Tremelimumab is being tested in an extensive clinical-trial programme in combination with Imfinzi in NSCLC, locally-advanced or metastatic urothelial carcinoma, head and neck cancer, liver cancer and blood cancers.

On April 24, 2018 Coherus BioSciences, Inc. (Nasdaq:CHRS), reported that its first quarter 2018 financial results will be released after market close on Thursday, May 10, 2018 (Press release, Coherus Biosciences, APR 24, 2018, View Source/phoenix.zhtml?c=253655&" target="_blank" title="View Source/phoenix.zhtml?c=253655&" rel="nofollow">View Source;p=RssLanding&cat=news&id=2344193 [SID1234525630]). Starting at 4:30 p.m. EDT, Coherus’ management will host a conference call to discuss the financial results and provide a general business update.

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After releasing first quarter 2018 financial results, we will post them on the Coherus BioSciences website at View Source." target="_blank" title="View Source." rel="nofollow">View Source

Conference Call Information
When: Thursday, May 10, 2018 at 4:30 p.m. ET
Dial-in: (844) 452-6826 (toll free) or (765) 507-2587 (International)
Conference ID: 2767588
Webcast: View Source
Please join the conference call at least 10 minutes early to register. The webcast will be archived on the Coherus website.

On April 24, 2018 Autolus Limited, a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the execution of a license agreement under which Autolus has acquired global rights from UCL Business plc (UCLB), the technology-transfer company of University College London (UCL), to develop and commercialize a novel CD19 chimeric antigen receptor (CAR) T cell therapy with novel targeting properties for the treatment of B cell malignancies (Press release, UCLB, APR 24, 2018, View Source [SID1234525647]).

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The product candidate, which we have designated as AUTO1, is an investigational therapy in which a patient’s T cells are genetically modified to express a novel CD19-specific CAR designed to reduce side effects related to cytokine release syndrome (CRS). CD19 is a protein expressed by B-cell lymphomas and leukaemias. CD19 CAR T cells have proven effective in treating leukaemia and lymphoma, with efficacy dependent on engraftment and expansion of CAR T cells. However, rapid activation and expansion of CAR T cells can result in CRS, which in some cases can be life-threatening, particularly for elderly patients and patients with higher tumour burden that have poor tolerance for toxicity. Furthermore, excessive activation of CAR T cells can lead to cell exhaustion and limit their persistence.

AUTO1 is currently the subject of two Phase 1 studies, one in paediatric acute lymphoblastic leukaemia (ALL) and the other in adult ALL*. AUTO1 has been designed to recognise CD19 with a fast-off binding kinetic, which allows CAR T cells to efficiently recognize cancer cells, inject cytotoxic proteins to initiate the natural self-destruction process present in all human cells and then rapidly dissociate from them in order to engage the next cancer cell – a process also known as serial killing. We believe that avoiding prolonged residence on targeted cells may minimize excessive activation of CAR- T cells and reduce toxicity and CAR T cell exhaustion. In a UCL Phase 1 clinical study (CARPALL) in paediatric ALL patients evaluating the properties of AUTO1, investigators observed levels of efficacy similar to those in other reported studies, without observing grade 3 or 4 CRS and without the need to administer immunosuppressive drugs. Data from the CARPALL study were presented at the 2017 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper)**.

Dr Martin Pule, Chief Scientific Officer of Autolus Limited and Senior Lecturer in Haematology at UCL, commented:"Current CARs in the clinic are designed with high affinity binders that can engage the CD19 target for an extended period of time. This can lead to excessive T cell activation and cytokine release, as well as exhaustion of the T cell.We developed a CD19 CAR that is designed to bind to its target with a fast on-rate but then releases quickly, which is more similar to naturally occurring T cell activity. The initial clinical data supports the premise that this kinetic profile reduces toxicity and increases CAR T cell engraftment."

Dr Christian Itin, Chief Executive Officer of Autolus Limited, added:"This licensing arrangement represents an exciting opportunity for Autolus as we continue to expand our broad pipeline of clinical-stage T cell programs, with clinical trials currently ongoing for five programmes in six indications. With AUTO1, we are collaborating with UCLB in an ongoing trial in adult ALL patients and also expect to leverage the improved safety profile of the CD19 binder in future generations of our programmed T cell therapies for the treatment of patients with B cell malignancies."

Cengiz Tarhan, Managing Director of UCLB, said:"The development of this product candidate represents the culmination of several years of research led by Martin Pule and his collaborators, drawing on funding from multiple government and charitable sources. UCLB is delighted to be able to partner with Autolus to support the continued development of this promising approach."

* Paediatric ALL "CARPALL Study": View Source and adult ALL "ALLCAR19 Study": View Source;
**Abstract: View Source;

Media Contact:

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Julia Wilson
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On April 24, 2018 Enzo Biochem, Inc. (NYSE: ENZ) and its subsidiary Enzo Life Sciences, Inc. reported that the Patent Trial and Appeal Board has denied a petition filed by Hologic, Inc. (Nasdaq: HOLX) for inter partes review, a procedure for challenging the validity of patent claims, against U.S. Patent 6,221,581. Enzo Life Sciences, Inc. is asserting U.S. Patent 6,221,581 in patent infringement litigation against Hologic, Inc., Grifols Diagnostic Solutions, Inc., and Grifols S.A. in the U.S. District Court for the District of Delaware (Press release, Enzo Biochem, APR 24, 2018, View Source [SID1234525631]).

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