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OBI Pharma Announces Acquisition of TH-3424 from Threshold Pharmaceuticals

On June 1, 2017 OBI Pharma, Inc., a Taiwan biopharma company (TPex: 4174), reported an agreement with Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) to acquire TH-3424, a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1c3 (AKR1C3) (Press release, OBI Pharma, JUN 1, 2017, View Source [SID1234525559]). The product will be renamed OBI-3424 effective immediately.

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OBI-3424 is a first-in-class prodrug that selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.

AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult to treat cancers. For example, hepatocellular carcinomas (HCC), which highly overexpress AKR1C3 in the majority of patients. OBI-3424 has demonstrated potent activities in preclinical models of HCC, including a model resistant to the standard of care treatment, sorafenib. AKR1C3 is adaptively upregulated in response to castration; therefore, castrate-resistant prostate cancer is another logical unmet need population where OBI-3424 will be tested. In addition, the US National Cancer Institute is performing preclinical evaluations of OBI-3424 for the potential treatment of T-cell acute lymphoblastic leukemia (T-ALL).

Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed to identify patients with other tumor types most likely to respond to treatment with OBI-3424, thereby offering the possibility for a streamlined clinical development strategy.

Under the terms of the agreement, Threshold will transfer to OBI Pharma its ownership rights as well as preclinical and manufacturing data for OBI-3424 in exchange for an undisclosed, upfront one-time payment. No further payments or future royalties are required. OBI Pharma will obtain Threshold’s global intellectual property as well as the commercial, developmental, and manufacturing rights to OBI-3424, except in certain specified countries in Asia (see footnote 1).

"OBI-3424 is an innovative anticancer drug that can preferentially deliver its payload to cancers that overexpress the activating enzyme, AKR1C3. AKR1C3 is highly overexpressed in a number of cancers that represent unmet medical needs, including hepatocellular carcinoma, castrate-resistant prostate cancer, and T-cell acute lymphoblastic leukemia. OBI-3424 offers the possibility of early efficacy read outs based on objective response rates in well-defined resistant patient populations," said Tillman Pearce, M.D., Threshold’s Chief Medical Officer.

"We will continue the pre-clinical work and hope that OBI-3424 develops into a solid treatment option for patients with cancers that express AKR1C3," said Amy Huang, General Manager of OBI Pharma, Inc. "This novel cancer therapeutic enhances our pipeline and moves us another step towards becoming a global cancer biopharma company. "

OBI Pharma plans to accelerate the development of OBI-3424, with an Investigational New Drug (IND) application filing with the U.S. Food and Drug Administration (FDA) planned for early 2018.

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(1) OBI obtains worldwide rights with the exception of the following countries: China, Hong Kong, Macao, Taiwan, Japan, South Korea, Singapore, Malaysia, Thailand, Turkey and India.

Debiopharm International SA Announces Results from Phase I Dose-Escalation Study of Debio 1347/CH5183284

On June 1, 2017 Debiopharm International SA (Debiopharm – www.debiopharm.com), part of Debiopharm Group, a Swiss-based global biopharmaceutical company, reported the results from the phase I dose-escalation study evaluating the compound Debio 1347/CH5183284 (FGFR 1,2,3 selective inhibitor). The data will be presented at the 53rd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting by Martin H. Voss, MD, Medical Oncology at the Memorial Sloan Kettering Cancer Center in New York.

"We are very pleased to have reached this milestone and to be able to see these very interesting and promising results presented at the upcoming ASCO (Free ASCO Whitepaper) meeting. Despite not reaching the MTD, we are confident to have reached the right dose for phase 2 – given the indicators of anti-tumor activity that we have seen", said Chris Freitag, VP Clinical Research & Development.

Oral Abstract Session: Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics
TITLE DATE AND TIME N°

Debio 1347, an oral FGFR inhibitor: Results from a first-in-human, phase I dose-escalation study in patients with FGFR genomically activated advanced solid tumors.

Sat, June 3, 1:15 – 1:27
#2500

About Debio 1347/CH5183284
Debio 1347/CH5183284, created by Chugai Pharmaceutical. Co., Ltd., is an orally available small molecule targeting FGFR 1, 2, 3 signaling pathways. Debiopharm International SA completed the dose escalation portion of the first-in-human phase I study. Debio 1347/CH5183284 had a manageable safety profile. Encouraging antitumor activity was seen in several tumor types, mainly in patients with FGFR2 or 3 gene alterations, including fusion events. Efficacy will be further explored in disease-specific and molecularly defined expansion cohort.

Atreca to Present at the Jefferies 2017 Global Healthcare Conference

On June 1, 2017 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported that Tito Serafini, Ph.D., President, Chief Executive Officer, and Co-Founder, will present at the Jefferies 2017 Global Healthcare Conference on Thursday, June 8, 2017 at 8:00 a.m. Eastern Time in New York, NY (Press release, Atreca, JUN 1, 2017, View Source [SID1234522952]). Dr. Serafini will provide an overview of Atreca’s technologies, programs and progress.

Eleven Biotherapeutics Announces Data and Safety Monitoring Board (DSMB) Recommendation to Continue Phase 3 Registration Trial with Vicinium™ in Non-Muscle Invasive Bladder Cancer Based on Review of Safety and Efficacy Data

On June 1, 2017 Eleven Biotherapeutics, Inc. (NASDAQ:EBIO), a late-stage clinical oncology company advancing a broad pipeline of novel product candidates based on its Targeted Protein Therapeutics (TPTs) platform, reported that its Phase 3 registration trial of Vicinium in non-muscle invasive bladder cancer (NMIBC) has exceeded 50% enrollment and that the independent Data and Safety Monitoring Board (DSMB) for the trial has recommended that the trial continue as planned (Press release, Eleven Biotherapeutics, JUN 1, 2017, View Source [SID1234519355]). The DSMB reviewed available data to assess the risk/benefit to patients on drug and recommended that the trial continue without modification.

"We are very pleased that the DSMB recommended we continue enrolling our Phase 3 trial after their review of available safety and efficacy data," said Stephen Hurly, President and Chief Executive Officer of Eleven Biotherapeutics. "Patients with Bacillus Calmette-Guérin (BCG) unresponsive NMIBC have limited therapeutic options and frequently require cystectomies to prevent disease progression. Bladder removal, however, is a serious and life-altering surgery associated with significant morbidity and mortality. Vicinium may offer patients a positive non-surgical risk/benefit profile versus the standard of care. We look forward to advancing our trial as we continue to gain important information about the activity of Vicinium in patients with NMIBC."

"Urologists are looking for new treatment options for their patients with NMIBC once they stop responding to BCG. Their patients want alternatives to cystectomy. However, the NMIBC treatment landscape has not seen meaningful advances in forty years," commented Arthur DeCillis, Chief Medical Officer of Eleven Biotherapeutics. "With this positive step behind us, we look forward to continuing our Phase 3 registration trial and to reporting topline 3-month data in the second quarter of next year."

Vicinium is a single protein anti-epithelial cell adhesion molecule (anti-EpCAM) antibody fragment fused with Pseudomonas Exotoxin A (ETA) that is designed to specifically target and deliver a potent anti-cancer payload directly into tumor cells. The ongoing Phase 3 registration trial is a single-arm study evaluating Vicinium in patients with high-grade NMIBC, who have previously received two courses of BCG and whose disease is now BCG-unresponsive. Eleven Biotherapeutics plans to enroll 134 patients, at over 70 centers in the United States and Canada. The trial’s primary endpoint is the complete response rate in patients with carcinoma-in-situ (CIS). Secondary endpoints include time to disease recurrence and event free survival. The Company expects to complete patient enrollment in the second half of 2017 and to report 3-month data in the second quarter of 2018.

MorphoSys Starts Phase 3 Trial of MOR208 plus Bendamustine in Patients with Relapsed or Refractory DLBCL

On June 1, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that the pivotal phase 3 part of the B-MIND clinical study of MOR208 has been opened for enrollment (Press release, MorphoSys, JUN 1, 2017, View Source [SID1234519341]).

The randomized, multicenter phase 2/3 study is designed to investigate the efficacy of MOR208 plus bendamustine versus rituximab plus bendamustine in patients with relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL) who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). DLBCL is the most common form of non-Hodgkin’s lymphoma. MOR208 is an investigational, Fc-enhanced monoclonal antibody directed against CD19 and is being developed for the treatment of patients with B cell malignancies.

"We are delighted that MOR208, as the first antibody from MorphoSys’s proprietary pipeline, has started pivotal phase 3 development," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "For patients with relapsed or refractory DLBCL who are not eligible for HDC and ASCT, current treatment options are limited. In our pivotal B-MIND study, we are therefore exploring MOR208 in combination with bendamustine, as a potential treatment alternative for this difficult-to-treat patient group".

Based on the available data from the phase 2 safety evaluation part of the B-MIND trial, the Independent Data Monitoring Committee (IDMC) supported the continuation of the trial as per protocol and the transition of the study into its pivotal phase 3 part.

Patients must have been treated previously with at least one but not more than three prior lines of therapy, including one anti-CD20 targeted therapy. The study is expected to enroll a total of approximately 330 patients in about 180 centers in Europe, Asia Pacific (APAC) and the USA.

The dosing of the first patient in the phase 3 part will trigger an undisclosed milestone payment to Xencor, Inc., from whom MOR208 was in-licensed in 2010. MorphoSys has worldwide rights to MOR208.

Detailed information on the trial can be found at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02763319).

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab(R)5574) is an Fc-enhanced monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. Furthermore, MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be a crucial component for B cell receptor (BCR) signaling.
MorphoSys AG is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. A phase 2 combination trial (L-MIND study) started in March 2016 and is designed to investigate the safety and efficacy of MOR208 in combination with lenalidomide in approximately 80 patients with relapsed/refractory DLBCL. The phase 2/3 B-MIND study was started in August 2016 and transitioned into its phase 3 pivotal part in June 2017 following a recommendation of the IDMC based on the available data from the phase 2 initial safety evaluation. The B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in relapsed/refractory DLBCL patients who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. Furthermore, in December 2016, a third phase 2 combination trial (COSMOS study) was started with MOR208 evaluating the antibody in patients with relapsed/refractory CLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib). Currently MOR208 is being studied in combination with idelalisib; a second study arm of MOR208 plus venetoclax is currently in preparation.