On June 15, 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 data from an ongoing Phase 1 study of Bruton’s tyrosine kinase (BTK) inhibitor BGB-3111 in patients with Waldenström’s macroglobulinemia (WM) at the 14th International Conference on Malignant Lymphoma (14-ICML) in Lugano, Switzerland (Press release, BeiGene, JUN 15, 2017, View Source [SID1234519560]). The updated Phase 1 data continue to demonstrate that BGB-3111 is well tolerated, with a very good partial response (VGPR) rate of 43% and with an overall response rate (ORR) of 90% in 42 efficacy-evaluable patients with a median follow-up time of 12.3 months.

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"The updated data continue to suggest that BGB-3111 is well tolerated in WM. Particularly notable is the VGPR rate of over 40% in an evaluable population of 42 patients. In addition, responses to BGB-3111 appear to deepen with time and to occur in patients both with and without MYD88 mutations. The rates of adverse event-related discontinuation and disease progression remain very low," commented Judith Trotman, MBChB, FRACP, FRCPA, Director of Clinical Research in Haematology at the Concord Repatriation General Hospital, Clinical Associate Professor of Medicine at the University of Sydney, and the lead author of the abstract.

"We are very pleased to update our Phase 1 data of BGB-3111 in patients with WM. The high rate of VGPRs observed to date may result in part from BGB-3111’s ability to completely and sustainably occupy BTK in both circulating and nodal lymphocytes. The VGPR rate also further supports the continued evaluation of BGB-3111 in its global, head-to-head Phase 3 study against ibrutinib in WM," 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 as monotherapy in 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 and relapsed/refractory WM. The ongoing dose-expansion phase is testing doses of 160 mg twice a day (BID) or 320 mg once a day (QD). As of March 31, 2017, 48 patients with WM were enrolled in the study. Responses were determined according to the modified Sixth International Workshop on WM (IWWM) criteria.

BGB-3111 was shown to be well tolerated with no discontinuation for BGB-3111-related toxicity to date. Adverse events (AEs) were generally mild in severity and self-limited. The most frequent AEs (>10%) of any attribution among 48 patients evaluable for safety were petechiae/purpura/contusion (35%), upper respiratory tract infection (31%), constipation (25%), diarrhea (19%), epistaxis (19%), nausea (17%), cough (15%), anemia (15%), headache (15%), neutropenia (13%), and rash (13%), all of which were grade 1 or 2 in severity except for grade 3 or 4 anemia and neutropenia (8% each) as well as grade 3 or 4 diarrhea and headache (2% each). Five serious AEs were assessed to be possibly related to BGB-3111; these included one case each of hemothorax, atrial fibrillation, colitis, febrile neutropenia, and headache. Among AEs of special interest, there were a total of three cases of atrial fibrillation (all grade 1 or 2), and one case of serious hemorrhage (hemothorax), defined as grade 3 or higher hemorrhage or central nervous system hemorrhage of any grade. Three events led to treatment discontinuation: one case each of bronchiectasis, prostate adenocarcinoma, and adenocarcinoma of pylorus.

At the time of the data cutoff, 42 patients were evaluable for response. Patients not evaluable for efficacy included two patients with less than 12 weeks of follow-up, three patients with IgM < 500mg/dl at baseline, and one patient with inaccurate baseline IgM due to cryoprotein. At a median follow-up of 12.3 months (4.4–30.5 months), the ORR was 90% (38/42 patients) and the major response rate was 76% (32/42 patients), with VGPRs in 43% (18/42) of patients and partial responses in 33% (14/42) of patients. There were two cases of disease progression.

Investor Call and Webcast Information

BeiGene will host an investor call and webcast to discuss the data presented at 14-ICML and its development program.

Date & Time: Friday, June 16, 2017, 2:00 PM CEST (8:00 AM EDT, 8:00 PM China Standard Time)

Dial-in Numbers: 1-845-675-0437 or 1-866-519-4004 (US), 400-620-8038 or 800-819-0121 (China), +852 30186771 (Hong Kong), or +65 67135090 (International)

Conference ID Number: 33044427

A live webcast and replay will be available on BeiGene’s investor website View Source The dial-in replay will be available approximately two hours after the conference and will be available for two days following the event. It can be accessed by dialing 1-646-254-3697 (US), 400-632-2162 (China), +852 30512780 (Hong Kong), or +61 2 8199 0299 (International).

About BGB-3111

BGB-3111 is a potent and highly selective investigational small molecule inhibitor of BTK (Bruton’s Tyrosine Kinase). BGB-3111 has demonstrated higher selectivity against BTK than ibrutinib (the only BTK inhibitor currently approved by the U.S. Food and Drug Administration and the European Medicines Agency) based on biochemical assays, higher exposure than ibrutinib based on their respective Phase 1 experience, and sustained 24-hour BTK occupancy in both the blood and the lymph node.

On June 15, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a preclinical pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported it has asked its contract research organization (CRO), Theradex Systems, Inc., to expand its engagement to include clinical sites in Poland for Moleculin’s planned Phase I/II clinical trial of Annamycin for the treatment of relapsed or refractory acute myeloid leukemia (AML) (Press release, Moleculin, JUN 15, 2017, View Source [SID1234519558]).

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"We have been working on ways to increase our rate of patient accrual once we start our planned clinical trial for Annamycin," commented Walter Klemp, Chairman and CEO of Moleculin, "and we have identified several promising sites in Poland. By expanding our engagement with Theradex, we help ensure tight coordination of clinical activity between the US and Poland."

Mr. Klemp continued: "If our IND is permitted, which must happen for clinical trials to begin, we intend to hit the ground running, and we believe Poland improves that capability. AML patients in Poland have less access to clinical trials than those in the US, which should make it easier for us to recruit relapsed or refractory AML patients who have received a fewer number of prior failed treatments and, as a result, may be less resistant to future treatments, and/or whose general health is less severely compromised. Work is already under way to identify a lead European Principal Investigator and to recruit the most appropriate clinical sites for the expansion."

On June 15, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX), reported updated clinical data from its Phase I/Ib trial of TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody in combination with TGR-1202 (umbralisib), the Company’s oral, next generation PI3K delta inhibitor, and bendamustine, in patients with Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) (Press release, TG Therapeutics, JUN 15, 2017, View Source [SID1234519555]). Data from this trial was presented today during a poster session at the 14th International Conference on Malignant Lymphoma (ICML).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "Relapsed and refractory DLBCL remains one of the most difficult to treat lymphoid malignancies, with a uniformly poor prognosis, particularly for patients with refractory disease who are not eligible for high-dose chemotherapy or stem-cell transplantation." Mr. Weiss continued, "The data presented today by Dr. Lunning supports our belief that the combination of TG-1101 (ublituximab) and TGR-1202 (umbralisib), our ‘U2 regimen’, with bendamustine is a highly active and well tolerated treatment for patients with aggressive lymphomas. We are excited to be able to rapidly bring this combination forward in the DLBCL arm of our randomized registration-directed UNITY-NHL program and hope to be enrolling patients into this cohort before the end of the summer."

Dr. Matthew Lunning, of the University of Nebraska Medical Center, stated, "I am extremely pleased with the durable responses seen with this novel triplet regimen, especially in patients with aggressive DLBCL who may not have been candidates for more intensive chemotherapy, transplantation, or CAR-T therapy, due to poor performance status or need for urgent therapy, a truly unmet medical need. Many patients had high-risk molecular features and some have obtained sustained responses. In addition to being highly active, the triplet regimen of U2-benda was very well tolerated, with a low incidence of Grade 3 or greater adverse events, particularly those that have been associated with the PI3K-delta class. I look forward to the possibility of testing this regimen earlier in relapsed and refractory DLBCL and am excited to see it advance into registration directed studies."

Highlights from today’s presentation include the following:

Poster Presentation: Combination of TGR-1202, Ublituximab, and Bendamustine is safe and highly active in patients with advanced DLBCL and Follicular Lymphoma (Abstract 277)

This poster presentation includes data from patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL) treated with the triple combination of TG-1101 (ublituximab), TGR-1202 (umbralisib) and bendamustine. Thirty-three patients were evaluable for safety of which 24 were evaluable for efficacy (9 patients were note evaluable; 7 were too early to evaluate and 2 patients were off study prior to an efficacy assessment: 1 non-related adverse event (AE) and 1 investigator decision). The triple combination appears well tolerated with no discontinuations for a treatment related AE. No events of pneumonitis and no Grade 3/4 transaminitis were reported. Twenty-one patients (64%) were refractory to prior treatment. Mean time on study was approximately 6 months.

Efficacy highlights from this poster include:

100% (4 of 4) ORR, including a 50% CR rate, observed in patients with relapsed DLBCL
50% (6 of 12) ORR, including a 42% CR rate, observed in patients with refractory DLBCL with durable CR and PR responses observed (PR on-going for > 16+ months)
88% (7 of 8) ORR, including a 50% CR rate, observed in patients with relapsed or refractory FL
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 15, 2017 Portola Pharmaceuticals Inc. (Nasdaq:PTLA) reported the presentation of interim data from a Phase 2a study evaluating cerdulatinib in patients with relapsed/refractory B-cell malignancies (Press release, Portola Pharmaceuticals, JUN 15, 2017, View Source [SID1234519554]). Cerdulatinib is an investigational oral, dual SYK/JAK kinase inhibitor for the treatment of relapsed/refractory B-cell and other hematological malignancies, specifically in patients who have not responded to prior therapies. The data were presented by Paul Hamlin, M.D., chief of the Medical Oncology Service at Memorial Sloan Kettering Basking Ridge during an oral presentation given earlier today at the International Congress on Malignant Lymphoma (ICML) in Lugano, Switzerland.

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The interim results presented at ICML demonstrated evidence of clinical activity in patients with relapsed/refractory (r/r) B-cell malignancies. To date, overall response rates are as follows:

12 out of 18 (67%) partial responses (PRs) in patients with r/r CLL/SLL
5 out of 9 (56%) PRs in patients with r/r FL
1 out of 7 (14%) PRs in patients with other r/r iNHL (marginal zone lymphoma and Waldenstrom macroglobulinemia)
A complete response (CR) was seen in the first r/r peripheral T cell lymphoma (PTCL) patient evaluated in the study
Results also showed that cerdulatinib was generally well-tolerated in these heavily pre-treated patients (at target drug levels). However, three patients at 35 mg BID achieved higher than expected drug concentrations and had severe adverse events (SAEs) including two grade 5 infections and one case of grade three pancreatitis. The dose was subsequently reduced to 30 mg BID and a PK monitoring strategy was implemented. This has resulted in an improved PK and safety profile without compromising clinical activity.

"While we continue to focus our efforts on gaining regulatory approval of our two lead programs, betrixaban and AndexXa (andexanet alfa), we are pleased that our third molecule, cerdulatinib, continues to show promising results in hematologic cancers — an area of great unmet need," said John Curnutte, M.D., Ph.D., executive vice president, research and development of Portola. "We believe these results of our Phase 2a trial further validate cerdulatinib’s potential to control relapsed/refractory B-cell malignancies by a differentiated mechanism of action, inhibiting two key cell signaling pathways that promote cancer. We anticipate an update on the ongoing study and a decision regarding future development by the end of 2017."

"Patients with relapsed/refractory CLL and NHL are difficult to treat and have limited options after failing standard therapy," said Dr. Hamlin. "Presently, there are few effective treatments for patients who have failed prior therapies. The interim results of this clinical trial are very encouraging, and cerdulatinib could represent an important treatment option for these patients if confirmed in further trials."

Additional detail on the interim Phase 2a data will be provided at the upcoming European Hematology Association (EHA) (Free EHA Whitepaper) 22nd Annual Congress from June 22-25, 2017.

About the Phase 1/2a Study
The open-label, multicenter, Phase 1/2a proof-of-concept study assessed the safety, pharmacokinetics, pharmacodynamics and clinical activity of oral cerdulatinib in patients with CLL and NHL. In the multi-dose, dose-escalation Phase 1 part of the study, cerdulatinib was administered orally once or twice daily in sequential dose cohorts at increasing dose levels until the maximum tolerated dose was identified. The clinical expansion cohorts in the Phase 2a part of the study are evaluating the safety and efficacy of cerdulatinib in cancer types identified based on results from the dose-escalation phase of the study. Up to 40 patients each will be enrolled in the clinical expansion cohorts including patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/ small lymphocytic leukemia (SLL), and indolent lymphomas such as follicular lymphoma (FL) and peripheral T cell lymphoma (PTCL).

About Cerdulatinib
Cerdulatinib is an oral, dual Syk-JAK inhibitor with a unique mechanism of action. It inhibits two key signaling pathways that promote cancer cell growth in certain hematologic malignancies: the B-cell receptor pathway via Syk and key cytokine receptors via JAK. With its dual pathway mechanism, cerdulatinib may be more effective in specific patients than a single pathway agent, such as those resistant to current therapies or those with known heterogeneous cellular mutations. Preclinical data suggested that cerdulatinib may have anti-tumor activity in patients who did not adequately respond to, or relapsed on, other treatments due to defined mutations.

On June 15, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH), reported results from the dose-escalation part of the ongoing Phase I study of IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas (CTCL), an orphan disease (Press release, Innate Pharma, JUN 15, 2017, View Source [SID1234519552]). IPH4102 is Innate Pharma’s wholly-owned, first-in-class anti-KIR3DL2 humanized therapeutic antibody, designed to trigger immune cell-mediated killing of CTCL cancer cells.

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25 patients, with a median age of 71 years old and a median number of four prior systemic treatments, were evaluable for safety (10 dose levels: 0.0001 to 10 mg/kg). The data from the trial indicate that IPH4102 was well tolerated with no dose-limiting toxicity. The maximum tolerated dose (MTD) was not reached. The majority of adverse events reported was typical for CTCL or reflected low grade infusion-related reactions.

As of May 10, 2017, 24 patients were evaluable for clinical activity. In this population, best global overall response rate (ORR) was 41.7% and disease control rate (DCR) was 91.7% across all dose levels. Best global ORR and DCR reached 47.4% and 89.5% respectively in patients with Sézary syndrome (SS, n=19). Among the 9 patients with SS who achieved clinical responses, one had a global complete response**. 5 complete responses were seen in blood and 2 in skin (resp. 26% and 11%). Median duration of response (DOR) was 8.2 months in all patients and not reached in patients with SS. Median progression free survival (PFS) was 9.0 months in all patients and 10.8 months in patients with SS (range from 0.9 to 17.2). Pruritus was significantly decreased in patients with clinical response.

Pharmacodynamic endpoints and molecular residual disease results are consistent with clinical activity results and show substantial elimination of neoplastic cells in skin and in blood.



Pierre Dodion, Chief Medical Officer of Innate Pharma, commented: "The data reported suggest that IPH4102 is very well tolerated in patients with advanced CTCL and shows promising signs of clinical activity. We are thrilled by these results, given that the trial included patients who had received all available treatment options. They give us confidence for the next steps of the development plan of IPH4102; the cohort expansion part of the trial is planned to start in Q3 2017 at the recommended Phase II dose. We are committed to bringing this potential new therapeutic option to patients and will be focused on working closely with the regulatory authorities during the coming months toward this goal."

Martine Bagot, Principal Investigator and Head of the Dermatology Department at the Saint-Louis Hospital, Paris, added: "We are very pleased with the results of the dose-escalation part of the trial. The profile of IPH4102 is very promising. Today, there is no satisfactory treatment and IPH4102 could be a new therapeutic option for CTCL patients in high medical need at advanced stages of the disease."

These data were presented in an oral presentation at the International Conference on Malignant Lymphoma (ICML) in Lugano on June 14. The presentation is available on the Company’s website