On June 14, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a clinical-stage biopharmaceutical company developing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported updated clinical data from an ongoing Phase 1 study of BTK inhibitor BGB-3111 in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in a poster at the 14th International Conference on Malignant Lymphoma (14-ICML) in Lugano, Switzerland (Press release, BeiGene, JUN 14, 2017, View Source [SID1234519547]). The updated Phase 1 data continue to demonstrate that BGB-3111 is well tolerated and highly active in CLL/SLL, with a high overall response rate (94%) and a very low treatment discontinuation rate (3%) at a median follow-up of 10.5 months for efficacy evaluation.

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"The updated data demonstrate that BGB-3111 has a high overall response rate in CLL and SLL, independent of poor-risk molecular features. It is also well tolerated, with only a single instance of toxicity-related discontinuation to date. Late-stage trials will further characterize BGB-3111’s clinical benefit and safety in CLL and SLL," commented John Seymour, MBBS, FRACP, PhD, Director of Cancer Medicine at Peter MacCallum Cancer Centre in Victoria, Australia, and the lead author of the presentation.

"The Phase 1 data on BGB-3111 in CLL and SLL have matured favorably since our last presentation at the 2016 American Society for Hematology Annual Meeting in December 2016. The rate and durability of response suggest that the complete and sustained BTK inhibition achieved with BGB-3111 results in high activity in CLL and SLL patients in the study to date. These results further affirm our plans to develop this agent for CLL and SLL both in China, where we have an ongoing pivotal trial, and globally," commented Jane Huang, MD, Chief Medical Officer, Hematology at BeiGene.

Summary of Results from the Ongoing Phase 1 Study

The multi-center, open-label Phase 1 trial of BGB-3111 in patients with B-cell malignancies is being conducted in Australia, New Zealand, South Korea, and the United States and consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which include treatment naïve (TN) and relapsed/refractory (R/R) CLL/SLL. The ongoing dose-expansion component is testing doses of 160 mg twice a day (BID) or 320 mg once a day (QD). As of March 31, 2017, 69 patients with CLL or SLL (18 TN, 51 R/R) were enrolled in the study.

BGB-3111 was shown to be well tolerated in CLL/SLL. The most frequent adverse events (AEs) (≥10%) of any attribution were petechiae/purpura/contusion (46%), fatigue (29%), upper respiratory tract infection (28%), cough (23%), diarrhea (22%), headache (19%), hematuria (15%), nausea (13%), rash (13%), arthralgia (12%), muscle spasms (12%), and urinary tract infection (12%); all of these events were grade 1 or 2 except for one case of grade 3 purpura (subcutaneous hemorrhage), which was the only major bleeding event. Additional adverse events of interest included one case of each grade 2 diarrhea and grade 2 atrial fibrillation. A total of 18 serious AEs (SAEs) occurred in 13 patients, with no SAE occurring in more than one patient. Only one patient discontinued treatment due to an AE, a grade 2 pleural effusion.

At the time of the data cutoff, 66 patients (16 TN and 50 R/R) had more than 12 weeks of follow-up and were evaluable for efficacy, and three other patients had less than 12 weeks of follow-up. After a median follow-up of 10.5 months (2.2-26.8 months), the overall response rate (ORR) was 94% (62/66) with complete responses (CRs) in 3% (2/66), partial responses (PRs) in 82% (54/66), and PRs with lymphocytosis (PR-Ls) in 9% (6/66) of patients. Stable disease (SD) was observed in 5% (3/66) of patients. The patient with pleural effusion discontinued treatment prior to week 12 and was not evaluable for response. There was one instance of Hodgkin’s transformation. In TN CLL/SLL, at a median follow-up time of 7.6 months (3.7-11.6 months), the ORR was 100% (16/16) with CRs in 6% (1/16), PRs in 81% (13/16) and PR-Ls in 13% (2/16) of patients. In R/R CLL/SLL, at a median follow-up time of 14.0 months (2.2-26.8 months), the ORR was 92% (46/50) with CRs in 2% (1/50), PRs in 82% (41/50), and PR-Ls in 8% (4/50) of patients. Stable disease was observed in 6% (3/50) patients.

On June 14, 2017 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported updated data from its Phase 1b expansion study of ARGX-110 in patients with different subtypes of relapsed/refractory cutaneous T-cell lymphoma (CTCL) and various disease stages, at the International Conference of Malignant Lymphoma (ICML) in Lugano, Italy (Press release, arGEN-X, JUN 14, 2017, View Source [SID1234519546]).

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"Analysis of the skin biopsies continues to strengthen the biological rationale of targeting CD70 with ARGX-110. Clinical activity was observed in patients across different CTCL subtypes (mycosis fungoides, Sézary syndrome, panniculitis-like TCL) and different disease stages whilst the drug shows a favorable safety and tolerability profile," commented Nicolas Leupin, Chief Medical Officer of argenx. "Improved pruritis was observed in some of the patients and will be further monitored to explore ARGX-110 modes of action in skin of CTCL patients."

The updated data from the currently ongoing Phase Ib study continue to show evidence of clinical and/or biological anti-tumor activity with ARGX-110. We observed partial response and stable disease, respectively, in three and seven out of 16 patients with highly relapsed/refractory CTCL and confirmed overexpression of CD70. Treatment-emerging adverse events were reported for six out of 16 patients. The poster presented at ICML can be accessed from the "Downloads" section of the argenx website.

In April 2017, argenx announced the initiation of a Phase II trial of ARGX-110 as a monotherapy in relapsed/refractory CTCL patients, in order to further examine the activity of the product candidate, using the optimal dose and biomarker panel determined during the Phase Ib trial.


About ARGX-110

ARGX-110 is a SIMPLE Antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors and severe autoimmune diseases. ARGX-110 is designed to: i) block CD70, ii) kill cancer cells expressing CD70 through antibody-dependent cellular phagocytosis and iii) restore immune surveillance against solid tumors (Silence K. et al. mAbs 2014; 6 (2):523-532). ARGX-110 is currently being evaluated in patients with hematological and solid tumors. ARGX-110 is currently being evaluated in a Phase II trial in combination with azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) and a Phase II trial in patients with relapsed/refractory CTCL. Preclinical work on ARGX-110 in AML was performed in collaboration with the Tumor Immunology Lab of Prof. A. F. Ochsenbein at the University of Bern, who won, together with Prof. Manz from the University Hospital of Zürich, the prestigious 2016 Otto Naegeli Prize for his breakthrough research on CD70/CD27 signaling with therapeutic potential for cancer patients.

On June 14, 2017 Modra Pharmaceuticals reported the initiation and the inclusion of the first patients in a Phase II study of its lead compound, ModraDoc006/r, in metastatic castration-resistant prostate cancer patients to investigate its safety, feasibility and pharmacokinetic profile (Press release, Modra Pharmaceuticals, JUN 14, 2017, View Source [SID1234519543]). ModraDoc006/r is a proprietary oral formulation of docetaxel (ModraDoc006) co-administered with boosting-agent ritonavir (r) to enhance the chemotherapy’s bioavailability. Chemotherapy remains an integral part of current cancer treatment regimens and achieving its oral delivery while retaining both efficacy and safety could significantly improve the therapeutic landscape for treating many types of cancer.

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"Modra Pharmaceuticals aims to apply its oral formulation technology in oncology, with an initial focus on taxane-based chemotherapy, to offer patients a better quality-of-life through a simpler and more effective route of administration. Our goal is to also provide clinicians with more options for prescribing combinatorial treatments in the rapidly developing landscape of cancer regimens," said Eric van der Putten, CEO of Modra Pharmaceuticals. "With the promising results we have seen in our Phase I studies and given the nature of our approach, we are highly confident that we can advance this compound quickly with the aim to initiate a pivotal program by early 2018."

The Phase II multi-center study will investigate safety and establish a feasible dosing regimen of ModraDoc006/r in chemotherapy naïve patients with metastatic castration-resistant prostate cancer for whom treatment with intravenous (IV) docetaxel is indicated. The study will enroll 20 patients and includes dose-escalation aiming to define the maximum tolerated dose that can be safely administered in a bi-daily weekly schedule without interruptions. Pharmacodynamics will be determined as secondary outcome measures. The first patients have already been treated as part of the trial.

Modra Pharmaceuticals’ technology has been developed to address an unmet need for improving patient convenience while maintaining chemotherapy’s effectiveness. As the lead program in the Company’s pipeline, ModraDoc006/r has successfully been tested in Phase I clinical trials in patients with solid tumors.

About ModraDoc006/r
ModraDoc006 is a proprietary tablet formulation of the widely-used chemotherapy drug docetaxel, which contains no toxic excipients and has excellent water solubility. ModraDoc006 is given in combination with ritonavir, an inhibitor of the drug efflux transporter protein P-glycoprotein (P-gp) and the liver enzyme cytochrome P450 3A4 (CYP3A4). Ritonavir increases the systemic bioavailability of docetaxel through inhibiting its metabolism and helps to circumvent side effects associated with IV-delivered docetaxel.

About metastatic Castration-Resistant Prostate Cancer (mCRPC)
mCRPC is an advanced form of prostate cancer and the fourth most common cause of cancer death overall. mCRPC is resistant to surgical treatment or androgen deprivation therapy, an antihormone therapy used to prevent the growth of prostate cancer cells. IV Docetaxel is currently the first-line treatment in this indication in chemotherapy naïve patients.

On June 14, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX), reported updated clinical data from its ongoing Phase I/Ib trial of TGR-1202 (umbralisib), the Company’s oral, next generation PI3K delta inhibitor, in combination with ibrutinib, a BTK inhibitor, in patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) (Press release, TG Therapeutics, JUN 14, 2017, View Source [SID1234519542]). This study is being run in collaboration with the Blood Cancer Research Partnership (BCRP) and Dana-Farber Cancer Institute (DFCI), in Boston, MA. Data from this trial were presented today by the Principal Investigator, Matthew S. Davids, MD, of Dana-Farber Cancer Institute, during an oral session at the 14th International Conference on Malignant Lymphoma (ICML), in Lugano, Switzerland.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We continue to be impressed with the safety, tolerability and activity of the combination of TGR-1202 and ibrutinib. With this all oral combination, we are seeing high response rates, including in those patients with prior PI3K inhibitor or ibrutinib exposure. Additionally, the combination was well tolerated with over 30 patients now treated and for durations upwards of 2.5 years in this independently run, investigator initiated study." Mr. Weiss continued, "We want to thank Dr. Davids and his collaborators at DFCI and the Leukemia & Lymphoma Society for leading this important investigator driven research. Dr. Davids’ research provides another important piece of information as we try to identify the best way to use these drugs, alone or in combination. These data complement the recently reported results at ASCO (Free ASCO Whitepaper) from the triple combination of TGR-1202, ibrutinib and TG-1101, our anti-CD20 monoclonal antibody, which showed that the three-drug combination was also well-tolerated and appeared to induce even higher rates of response, with 100% ORR by iwCLL criteria and deeper responses with 26% of the CLL patients achieving a CR. We look forward to continuing to explore these combinations to drive better outcomes for patients."

Highlights from today’s presentation include the following:

Oral Presentation: Updated results of a multicenter phase I/Ib study of TGR-1202 in combination with ibrutinib in patients with relapsed or refractory MCL or CLL (Abstract #040)

This oral presentation includes data from patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Mantle Cell Lymphoma (MCL) treated with TGR-1202 in combination with ibrutinib. 32 patients were evaluable for safety (18 CLL patients and 14 MCL patients), of which 31 patients were available for efficacy (17 CLL patients and 14 MCL patients). CLL patients had a median of 1.5 prior lines of therapy (range 1-6), with 2 patients receiving prior ibrutinib and 4 receiving prior PI3K inhibitors. MCL patients had a median of 3 prior lines of therapy (range 2-5), with 2 patients also receiving prior ibrutinib.

Highlights from this oral presentation include:

94% (16 of 17) of CLL patients achieved a Complete Response (CR), Partial Response (PR), or a Partial Response with lymphocytosis (PR-L), with 1 patient achieving a CR and 3 additional patients with radiographic CR
All 3 patients with prior PI3K inhibitor therapy that were evaluable for efficacy, and 1 of the 2 patients with prior ibrutinib exposure responded
1-year progression free survival (PFS) for CLL is 88% and overall survival (OS) at 1-year is 94%, (n=17), with the longest patient on study 29.5+ months
79% (11/14) ORR in patients with MCL, including 1 CR and 1 additional radiographic CR, with marked clinical benefit observed in two additional patients
Median PFS and OS for MCL is 8.4 and 11.6 months, respectively (n=11)
The combination appears well tolerated across all patients with no grade 3/4 transaminitis (liver toxicity), diarrhea, colitis or pneumonitis observed
PRESENTATION DETAILS:

The above referenced presentation is now available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 14, 2017 Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE:OXB), a leading gene and cell therapy group, reported the findings reported by Novartis on its global multi-centre Phase II JULIET study evaluating the efficacy and safety of CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor T cell (CAR-T) therapy, in adult patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL) (Press release, Oxford BioMedica, JUN 14, 2017, View Source [SID1234519541]). The study met its primary objective at interim analysis.

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Oxford BioMedica is the sole manufacturer of the lentiviral vector expressing CTL019 for Novartis. The commercial launch of CTL019 is anticipated by Novartis later this year and Oxford BioMedica will receive undisclosed royalties on potential future sales of Novartis CAR-T products.

The findings were presented during an oral session at 15:40 CET on Wednesday 14th June 2017 at the 14th International Conference on Malignant Lymphoma (ICML) meeting (Abstract #007).

Novartis reported the interim analysis of the global multi-centre Phase II JULIET study which showed a 3-month Overall Response Rate (ORR) of 45% (23 of the 51 patients evaluated), with 37% achieving a Complete Response (CR) and 8% achieving a Partial Response (PR), respectively. CR remained stable from three months through data cut off among the patient group. Among 51 patients with >3 month follow-up or earlier discontinuation, best ORR was 59% (95% CI, 44%-72%; P<0.0001) with 43% achieving CR and achieving 16% PR. CR and PR rates at 3 months were 37% and 8% respectively. Cytokine Release Syndrome (CRS) occurred in 57% of infused patients (17% grade 3, 9% grade 4); no CRS associated deaths occurred. No cerebral oedema was reported. Three patients died from disease progression, within 30 days of infusion. No deaths were attributed to CTL019. The abstract is available online here: View Source

The overall response rate seen in this early analysis is impressive for these heavily pre-treated patients with relapsed/refractory DLBCL, who have limited treatment options. The full JULIET primary analysis is expected to be available later this year and will serve as the basis for US and EU regulatory submissions.

John Dawson, Chief Executive Officer of Oxford BioMedica, commented: "We are pleased that Novartis has reported these additional strong data with CTL019 in another indication, r/r DLBCL, which is a much larger target patient population than for r/r ALL. We continue to work closely with Novartis in delivering the lentiviral vector across their CTL019 franchise, a product group described earlier this year, by Novartis, as having "blockbuster" potential."