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;

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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 Perrigo Company plc (NYSE; TASE: PRGO) reported that it will release its first quarter calendar year 2018 financial results on Tuesday, May 8, 2018 (Press release, Perrigo Company, APR 24, 2018, View Source [SID1234525645]). The Company will host a conference call beginning at 8:30 a.m. (EDT).

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The conference call will be available live via webcast to interested parties in the investor relations section of the Perrigo website at View Source or by phone at 877-248-9413, International 973-582-2737, and reference ID #6366917. A taped replay of the call will be available beginning at approximately 12:00 p.m. (EDT) Tuesday, May 8, until midnight Day, May 18, 2018. To listen to the replay, dial 800-585-8367, International 404-537-3406, and use access code 6366917.

The Company also announced that it will present at the Deutsche Bank 43rd Annual Healthcare Conference at 1:30 PM EDT on Wednesday, May 9, 2018. Interested parties can access the presentation webcast at View Source.

On April 24, 2018 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO FR0010095596), a biotechnology company specializing in the development of innovative drugs in oncology, notably against rare or resistant forms of cancer, reported the initiation of DRIIV (DNA Repair Inhibitor administered IntraVenously) phase I clinical trial of AsiDNA, its "first-in-class" DNA repair inhibitor (Press release, Onxeo, APR 24, 2018, View Source [SID1234525644]). The aim of the study is to assess AsiDNA safety profile and identify its optimal clinical dose, as well as determine its active dose at the tumor level, in patients with advanced solid cancer.

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First patient has been enrolled and dosed with AsiDNA.

AsiDNA has a unique and innovative mechanism of action that inhibits the repair of tumor DNA damages through a decoy process by activating the enzymes involved in the signaling and repairing of tumor DNA lesions and harnessing them, thus making them unable to repair the tumor damages, which leads to the mitotic death of the cell.

The DRIIV study is being conducted at three of the most prestigious centers in France and Belgium and interim results are expected in the second half of 2018.

"The DNA-damage response approach to cancer treatment is a highly compelling approach which has been already validated with the approval of PARP inhibitors, which belongs to the same general class of DDR. AsiDNA has a unique mechanism of action and the potential to provide patients with an attractive therapeutic option. I look forward to further evaluating AsiDNA in this important clinical trial," said Professor Christophe Le Tourneau of the Institut Curie in Paris, principal investigator of DRIIV.

"The initiation of DRIIV represents a significant milestone in the development of this unique asset and in enhancing the therapeutic potential of AsiDNA," said Judith Greciet, CEO of Onxeo. "Importantly, while AsiDNA has previously shown clinical activity when injected directly into the tumor, demonstrating similar activity via systemic administration will provide the opportunity to target a vast range of cancers. We look forward to evaluating AsiDNA in this phase I clinical trial in order to establish the clinical benefit of this promising product candidate when administered systemically, which represents a strong value catalyst for this key asset."

Olivier de Beaumont, Chief Medical Officer of Onxeo, added, "Thanks to the pre-clinical data generated to date, we have established the optimal clinical trial protocol for this phase I study and we look forward to conducting the DRIIV study with experienced oncology investigators. DRIIV is the first step in men that will enable us to effectively characterize AsiDNA’s safety profile and determine the optimal clinical dose in order to further develop AsiDNA, whether combined with other anticancer agents or as a monotherapy."

On April 24, 2018 Mirati Therapeutics, Inc. (Nasdaq: MRTX) (the Company or Mirati), a clinical-stage targeted oncology company, reported that a progress update on its lead development programs and announced updated, positive clinical trial data for sitravatinib, a spectrum selective kinase inhibitor, and mocetinostat, a class I and IV HDAC inhibitor (Press release, Mirati, APR 24, 2018, View Source [SID1234525643]). The Company has been evaluating sitravatinib and mocetinostat in separate Phase 2 clinical trials in combination with checkpoint inhibitor therapy in non-small cell lung cancer (NSCLC) patients whose disease had progressed following prior treatment with a checkpoint inhibitor. Both clinical trials have generated encouraging preliminary data demonstrating the potential to overcome resistance to checkpoint inhibitor therapy.

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"The majority of NSCLC patients either do not respond to checkpoint inhibitor therapy or experience disease progression following treatment. These patients have limited treatment options and generally experience poor outcomes in response to standard of care chemotherapy," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer. "The preliminary data from our Phase 2 study of sitravatinib plus nivolumab continue to highlight the promise of this combination to overcome resistance to initial checkpoint inhibitor therapy and provide a meaningful treatment option for this large and underserved patient population."

Sitravatinib is being evaluated in a Phase 2 study in combination with nivolumab (OPDVIO), an anti-PD-1 checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with a checkpoint inhibitor. As of the data cutoff date of March 31, 2018:

23 patients were evaluable for response with at least one radiographic scan

Six patients achieved a Partial Response (PR) (four confirmed and two unconfirmed)

1Five of the six patients with PRs remain on study, including both patients with unconfirmed PRs; the longest treatment duration exceeds 50 weeks and is ongoing

The other patient with a PR progressed following a treatment duration that exceeded 40 weeks

19 of 23 patients demonstrated tumor reductions

To date, the combination has been well-tolerated and most adverse events (AEs) reported by investigators were Grade 1 or 2.
"The responses and duration of treatment seen with the combination of sitravatinib and a checkpoint inhibitor are very promising, notably because these patients had relapsed following prior checkpoint inhibitor therapy," said Alexander Spira, M.D., Ph.D., Director of the Virginia Cancer Specialists Research Institute. "The trial is enrolling well, and we have been pleased with the favorable tolerability of the combination."

Enrollment is accelerating, and 45 patients have been enrolled. Correlative analyses of peripheral blood and tumor tissue biomarkers are ongoing. The Company is planning to present more mature data at an oncology conference later this year. The Company expects to meet with regulatory authorities in the second half of 2018 to discuss plans for registration.

In a separate Phase 2 study, mocetinostat is being evaluated in combination with durvalumab (IMFINZI), an anti-PD-L1 checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with a checkpoint inhibitor. As of the data cutoff date of March 31, 2018:

23 patients were evaluable for response with at least one radiographic scan

Three patients achieved a PR (two confirmed and one unconfirme

All three patients with PRs remain on study; the longest treatment duration exceeds 44 weeks and is ongoing
8 of 23 patients demonstrated tumor reductions.

To date, the combination has been well-tolerated, and most AEs reported by investigators were Grade 1 or 2.
31 patients have been enrolled in this ongoing trial and the Company plans to present more mature data at an oncology conference later this year.
Mirati also provided an update on the Phase 1b expansion trial for sitravatinib as a single agent. Interim clinical data will be presented in a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 1 – 5, 2018 in Chicago, Illinois. The presentation, titled "Evaluation of the spectrum selective RTK inhibitor sitravatinib in renal cell carcinoma (RCC) refractory to anti-angiogenic therapy" will report data from patients with RCC treated with single agent sitravatinib.

In that same Phase 1b trial of single agent sitravatinib, enrollment continues in the cohorts of patients whose tumors harbor CBL, CHR4Q12 and RET genetic alterations in NSCLC and other tumor types. The Company plans to present more mature data for these patients at an oncology conference later this year.

MRTX849, the Company’s small molecule mutation-selective KRAS G12C inhibitor, continues to advance towards a planned Investigational New Drug (IND) submission in the fourth quarter of 2018, with the potential to generate early proof-of-concept clinical data in 2019.

2

About Sitravatinib

Sitravatinib is a spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being tested in combination with nivolumab (OPDIVO), an anti-PD-1 checkpoint inhibitor, in NSCLC patients who have experienced documented disease progression following treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation.

Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion trial enrolling patients whose tumors harbor CBL, CHR4Q12 and RET genetic alterations in NSCLC and other solid tumors.

About Mocetinostat

Mocetinostat is a selective Class I and IV HDAC inhibitor. Inhibition of histone acetylation is predicted to enhance the recognition of tumor cells by anti-tumor T cells and reverse immunosuppressive factors in the tumor microenvironment. The Company is conducting a Phase 2 study of mocetinostat in combination with durvalumab (IMFINZI), an anti-PD-L1 checkpoint inhibitor, in NSCLC patients who have experienced disease progression following prior treatment with a checkpoint inhibitor.

About MRTX849

MRTX849 is an orally-available small molecule that potently and selectively inhibits a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MTRX849 has demonstrated complete regression of KRAS G12C-positive human tumors implanted in mice. IND-enabling preclinical studies are underway, and an IND submission is expected in the fourth quarter of 2018, with early clinical proof-of-concept anticipated in 2019.