On April 16, 2018 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that initial data from the Phase 1 GARNET trial of TSR-042 (anti-PD-1 antibody) in patients with microsatellite instability high (MSI-H) endometrial cancer and non-small cell lung cancer (NSCLC) presented during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, TESARO, APR 16, 2018, View Source [SID1234525363]).

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"Preliminary results from GARNET presented today at AACR (Free AACR Whitepaper) are the first clinical data from expansion cohorts for TSR-042, our anti-PD-1 antibody," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "These results demonstrate the clinical activity of TSR-042 and support our unique patient-centric dosing regimen that includes dosing every 6 weeks. We expect to complete enrollment in the MSI-H endometrial cohort of the GARNET trial by the end of the year. A regulatory submission for TSR-042 is planned in 2019. The breadth of TESARO’s immuno-oncology portfolio, which also includes antibodies targeting TIM-3 and LAG-3, enables us to evaluate both monotherapy and novel combination approaches with a goal of providing transformative therapies for people living with cancer."

Preliminary Activity in MSI-H Endometrial Cancer and Non-Small Cell Lung Cancer
GARNET is a multicenter, open-label, Phase 1 dose-escalation study designed to assess the safety, pharmacokinetics, pharmacodynamics, and clinical activity of TSR-042 in patients with advanced solid tumors. Part 1, a weight-based dose escalation study, and part 2A, a fixed-dose safety study, of GARNET have been completed. The ongoing part 2B expansion portion of GARNET is evaluating TSR-042 at a dose of 500 milligrams every 3 weeks for the first 4 cycles, and 1000 milligrams every 6 weeks thereafter in four open cohorts: MSI-H endometrial cancer, MSI-high non-endometrial cancer, MSS endometrial cancer and NSCLC. Data presented at AACR (Free AACR Whitepaper) included efficacy data from the cohorts of patients with MSI-H endometrial cancer and NSCLC from part 2B of the trial.

At the time of data cutoff, 15 patients with MSI-H endometrial cancer and 24 patients with NSCLC had at least 1 tumor assessment. Among the 15 patients with MSI-H endometrial cancer, 7 had partial responses by immune related RECIST (irRECIST) criteria (ORR 47%). Eleven patients continue on therapy, including one patient with a partial response who has thus far received over 42 weeks of TSR-042. Three additional patients (20%) had stable disease.

Among the 24 patients with NSCLC, 7 had partial responses by irRECIST criteria (ORR 29%). Twelve patients continue on therapy, including one patient with a partial response who has thus far received over 36 weeks of TSR-042. Ten additional patients had stable disease (42%), one of whom has continued treatment for over 36 weeks.
Preliminary safety findings among the 120 evaluable patients (including patients with MSI-H endometrial, NSCLC, and other tumor types) indicate TSR-042 is well-tolerated. Grade ≥3 treatment-related treatment-emergent adverse events (TEAEs) were reported in 9 of 120 patients (7%).
Serum concentrations of TSR-042 observed 6 weeks after the 1000 milligram dose were comparable to those observed 3 weeks after the 500 milligram dose, and maximal receptor occupancy was maintained throughout the 6-week dosing interval.

The GARNET study is intended to support a Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA) for patients with MSI-H cancers in 2019.
TESARO Poster Presentations at AACR (Free AACR Whitepaper) (all times local)

Immuno-oncology
Monday, April 16, 2018, 8:00 AM to 12:00 PM
Preliminary safety, efficacy and PK/PD characterization from GARNET, a phase I clinical trial of the anti-PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced NSCLC or MSI-H endometrial cancer
Poster Session, Abstract: CT053, Location: Exhibit Hall A, Poster Section 42, Poster Board 6
Monday, April 16, 2018, 8:00 AM to 12:00 PM
Checkpoint inhibitor signatures across endometrial cancer histologies
Poster Session, Abstract: 1687, Location: Exhibit Hall A, Poster Section 31, Poster Board 12
Monday, April 16, 2018, 8:00 AM to 12:00 PM
Simultaneous measurement and significance of PD-1, LAG-3 and TIM-3 expression in human solid tumors
Poster Session, Abstract: 1681, Location: Exhibit Hall A, Poster Section 31, Poster Board 6
Monday, April 16, 2018, 1:00 PM to 5:00 PM
Investigation of the expression profile and functional role of PD-1, TIM-3 and LAG-3 in human tumors
Poster Session, Abstract: 2722, Location: Exhibit Hall A, Poster Section 32, Poster Board 14
Wednesday, April 18, 2018, 8:00 AM to 12:00 PM
Characterization of tumor growth and immune microenvironment in humanized NOG-EXL mice implanted with A549, MDA-MB-436 and A375 cells
Poster Session, Abstract: 5690, Location: Exhibit Hall A, Poster Section 31, Poster Board 26

About GARNET
The ongoing Phase I GARNET trial is evaluating TSR-042 as monotherapy in patients with advanced solid tumors. GARNET included a weight-based dose escalation study (Part 1) and a fixed-dose safety study (Part 2A), both of which have been completed. Results of these studies were used to determine the recommended Phase 2 dose (RP2D; 500 mg Q3W for the first 4 cycles then 1000 mg Q6W). The study is now enrolling patients with MSI-H endometrial cancer, MSI-H non-endometrial cancer, MSS endometrial cancer, and NSCLC into four large expansion cohorts.

About TSR-042
TSR-042 is an investigational humanized anti-programmed death (PD)-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and effectively blocks its interaction with the ligands PD-L1 and PD-L2. TSR-042 is the only anti-PD-1 therapy administered as monotherapy every 3 weeks for 4 doses then every 6 weeks thereafter. TSR-042 was developed as part of the collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3 (TSR-075).

On April 16, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that preliminary clinical data from an ongoing Phase 1 trial of its investigational PARP inhibitor pamiparib in Chinese patients with locally advanced or metastatic high-grade non-mucinous ovarian cancer (HGOC), including fallopian cancer, or triple-negative breast cancer (TNBC), who had disease progression following at least one line of chemotherapy were presented at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held in Chicago (Press release, BeiGene, APR 16, 2018, View Source;p=RssLanding&cat=news&id=2342698 [SID1234525331]). Data presented from the dose-escalation phase of the ongoing Phase 1 trial confirmed the recommended Phase 2 dose (RP2D) of 60mg twice daily (BID) in Chinese patients and demonstrated that pamiparib showed antitumor activity and was generally well tolerated in these patients.

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"In these heavily pre-treated patients with ovarian and breast cancers, the preliminary results support the recommended pamiparib dosing regimen and demonstrated antitumor activity, including partial responses in platinum-resistant or refractory patients with ovarian cancer. We saw no dose-limiting toxicities and found pamiparib to be generally well tolerated among these patients," said Binghe Xu, M.D., Director of the Department of Medical Oncology, at the Cancer Hospital, Chinese Academy of Medical Sciences in Beijing, China, and the lead author of the poster presentation.

"In China, there are no currently approved PARP inhibitors, yet there are an aggregate of approximately 75,000 new cases of ovarian cancer1 and triple-negative breast cancer diagnosed each year1,2, and it is estimated that between 25 and 30 percent of ovarian cancer3 and between 15 and 204 percent of triple-negative breast cancer patients harbor a germline mutation in BRCA1/2 and therefore may benefit from a PARP inhibitor. We look forward to advancing pamiparib’s development in China as well as initiating a global Phase 3 trial," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology of BeiGene.

Summary of Results from the Ongoing Phase 1 Trial
This open-label, multi-center Phase 1 dose-escalation trial of pamiparib (NCT03333915) was designed to confirm RP2D and to evaluate its safety, tolerability and antitumor activity in Chinese patients with locally advanced or metastatic HGOC, including fallopian and primary peritoneal cancer, or patients with TNBC. Patients were dosed at 20mg, 40mg, or 60mg BID. As of September 25, 2017, 15 female patients were enrolled, nine with HGOC and six with TNBC. Nine patients received four or more prior lines of therapies. All nine patients with HGOC were platinum-resistant (n=8) or refractory (n=1). Seven patients had a confirmed BRCA1/2 mutation (BRCAm), including five patients with HGOC and two patients with TNBC and the remaining patients had BRCA 1/2 wildtype (BRCA-WT). The median duration of treatment was 2.5 months (range: 8-260 days).

Pamiparib was shown to be generally well tolerated. No dose-limiting toxicities were reported across the dose range, with RP2D confirmed as 60mg BID. Asthenia (n=12) and nausea (n=12) were the most commonly reported treatment-emergent adverse events (AE). Severity of all adverse events was grade 3 or less. Overall, three patients experienced a serious AE (grade 2 abdominal infection, n=1; grade 3 pleural effusion, n=1; grade 3 ileus, n=1), none of which were considered related to treatment. Two of the serious AEs led to treatment withdrawal (abdominal infection, n=1; pleural effusion, n=1).

As of September 25, 2017, 13 of the 15 patients were evaluable for antitumor activity; five patients remained on treatment. Two of the nine HGOC patients achieved a confirmed partial response including one platinum-refractory patient with BRCA wildtype status and one platinum-resistant patient with BRCA1/2 mutation, six HGOC patients had stable disease (BRCAm, n=4 and BRCA-WT, n=2) and one patient discontinued before the first radiographic assessment. Of the six treated TNBC patients, five (BRCAm, n=1, BRCA-WT, n=4) experienced disease progression and one patient (BRCAm) discontinued before the first radiographic assessment. Four of these evaluable TNBC patients were BRCA-WT and all experienced disease progression during the previous platinum-based chemotherapy.

About Pamiparib
Pamiparib (BGB-290) is an investigational inhibitor of PARP1 and PARP2 which has demonstrated pharmacological properties such as brain penetration and PARP–DNA complex trapping in preclinical models. Pamiparib is being evaluated in a pivotal clinical trial in China. It is currently in global clinical development as a monotherapy, and in combination with other agents, including BeiGene’s investigational anti-PD1 antibody, tislelizumab (BGB-A317), for a variety of solid tumor malignancies.

On April 16, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that it has entered a new worldwide collaboration with Bristol-Myers Squibb Company on a program to develop and commercialize Factor XIa (FXIa) inhibitors, including BMS-986177, for the prevention and treatment of major thrombotic conditions (Press release, Johnson & Johnson, APR 16, 2018, View Source [SID1234525347]). Under the agreement, Janssen Pharmaceuticals, Inc. and Bristol-Myers Squibb Company will advance BMS-986177 into Phase 2 clinical trials and establish a broad development program across multiple therapeutic indications.

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The development of novel oral anticoagulants has been a major step forward in the prevention and treatment of thrombosis. The goal for next-generation anticoagulants is to achieve the same efficacy as the current standard of care while substantially lowering the risk of bleeding. Early clinical research has shown that

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FXIa inhibition has the potential to reduce the risk of thrombotic events with a significantly lower risk of bleeding compared to currently available therapies.

"Janssen has built deep knowledge in the anticoagulation space through our extensive experience researching and developing innovative cardiovascular therapies," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular and Metabolism, Janssen Research & Development, LLC. "We look forward to applying our expertise to this collaboration with Bristol-Myers Squibb to explore the full potential of BMS-986177 through Factor XIa inhibition to provide a wider safety window for anticoagulation than current therapies."

"With the addition of a Factor XIa inhibitor program to our pipeline, Janssen continues to live up to our long-standing commitment of working tirelessly to bring truly transformational therapies to patients worldwide," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "With this new collaboration we have the potential to improve the standard of care for patients with cardiovascular conditions characterized by pathologic thrombosis."

The companies will share development costs and commercial profits and losses. Additional terms of the agreement were not disclosed

On April 16, 2018 VBL Therapeutics (NASDAQ:VBLT) reported that its presented a late-breaking study demonstrating a novel bi-specific antibody that induces immune-cell mediated killing of cancer cells through binding to a tumor membrane receptor, MOSPD2 (Press release, VBL Therapeutics, APR 16, 2018, View Source [SID1234525364]). Data are presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting in Chicago, Illinois

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.
"Selective targeting of tumor cells is challenging, as it requires a tumor-specific receptor, or process, that can be attacked without compromising safety. Our new data demonstrate that different solid tumors show high expression of MOSPD2 as it likely supports their ability to invade and metastasize. Our bi-specific antibody is taking advantage of this tumor-specificity to induce killing of tumor cells. We continue to advance our exciting VB-600 series of antibodies as drug candidates for oncology and inflammatory indications," said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics.

VBL research has identified MOSPD2 (Motile Sperm Domain-containing Protein 2) as a protein involved in cell motility. Previously, the Company published data on the involvement of MOSPD2 in immune cell migration, and new data presented today at AACR (Free AACR Whitepaper) show high and selective MOSPD2 expression by multiple tumor types along with involvement of MOSPD2 in tumor cell invasiveness. In addition, a novel bi-specific antibody that was engineered to bridge interaction of T-cells with tumor cells, via binding to the T-cell protein CD3 and the tumor receptor MOSPD2, induced T-cell activation and resulted in the killing of cancer cells in a pre-clinical setting.
These data provide proof-of-concept for the use of antibody-mediated killing of MOSPD2-expressing cancer cells, with potential applicability to solid tumors and myeloid malignancies. VBL is developing its VB-600 series of antibodies targeting MOSPD2 for oncology and inflammatory applications.
For VBL’s poster presentation at AACR (Free AACR Whitepaper) kindly see the following link.

On April 16, 2018 Only a couple weeks after Takeda Pharmaceuticals reported it was interested in buying Shire, Shire sells its oncology business to France’s Servier for $2.4 billion (Press release, BioSpace, APR 16, 2018, View Source [SID1234525333]).

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It’s possible the sale will make Shire less desirable for Takeda, since Shire’s oncology business was part of the rationale for buying the company. It’s also possible it will make it more desirable by dropping the price slightly. Reuters notes, "The [Servier} deal suggests there is value locked up within Shire’s portfolio—despite a dismal share price performance in the past two years—as its management braces for a possible $50-billion bid battle with Japan’s biggest drugmaker."

Shire has suggested the proceeds from the sale may be returned to shareholders via a buyback. It also indicated that further sales of non-strategic assets were a possibility.
Shire is making it clear that is began looking to sell its oncology business in December and began the sale process in January. In other words, they want it understood that they didn’t quickly sell off the cancer unit to fend off an unwanted Takeda acquisition.

Under UK acquisition laws, Takeda has until April 25 to announce an official bid. The market value of Shire is about $47 billion. Reuters writes, "Buying Shire would be transformational for Takeda but would be a huge financial stretch, since the company is worth around $10 billion more than the Japanese group. Shire also had debt of around $19 billion as of the end of 2017."

Shire’s oncology business includes products such as Oncaspar (pegaspargase), part of a multi-agent treatment for acute lymphoblastic leukemia (ALL) and ex-U.S. rights to Onivyde (irinotecan pegylated liposomal formulation), part of a multi-agent treatment for metastatic pancreatic cancer after gemcitabine-based therapy, and Calaspargase Pegol (Cal-PEG), which is currently under review by the U.S. Food and Drug Administration (FDA) for the treatment of ALL and early stage immuno-oncology pipeline collaborations.

"This transaction is a key milestone for Shire, demonstrating the clear value embedded in our portfolio," said Flemming Ornskov, Shire’s chief executive officer, in a statement. "While the Oncology business has delivered high growth and profitability, we have concluded that it is not core to Shire’s longer-term strategy. We will continue to evaluate our portfolio for opportunities to unlock further value and sharpen our focus on rare disease leadership with selective disposals of non-strategic assets."
Last year the Oncology business created revenues of $262 million.

If Takeda does make an official bid for Shire, this sale might make it slightly more affordable. Last year Takeda acquired Ariad Pharmaceuticals for $4.7 billion. "Shire’s decision to buy back shares may also indicate a positive view of the bid, since increasing shareholder returns would make it easier to get approval for a deal, Kazuyoshi Saito, a senior analyst for Iwai Cosmo Securities Co." told Bloomberg in a phone interview. "I have an impression that Takeda and Shire are heading in the same direction," Saito said.

Meanwhile, buying Shire’s oncology business bolster’s Servier’s presence in oncology. Olivier Laureau, Servier Group President, said in a statement, "The acquisition of Shire’s oncology franchise enables Servier to meet its strategic ambitions to become a global key player in oncology. As an essential step in the evolution of the Group, this acquisition allows us to establish a direct commercial presence in the United States, the world’s leading pharmaceuticals market, and to strengthen our portfolio of marketed products in the territories where Servier is already present. Our goal is to bring these treatments to greater numbers of cancer patients around the world. We thoroughly look forward to welcoming Shire’s oncology teams who will join Servier after the closing."