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BioInvent update on clinical and preclinical drug programs

On December 16, 2015 BioInvent International (OMXS: BINV) reported that it is providing an update on its clinical and preclinical drug programs (Press release, BioInvent, DEC 16, 2015, http://www.bioinvent.com/media-centre/press-releases/release/?ReleaseID=6B8448BB1FD836C4 [SID:1234508590]). Several positive interactions with regulatory authorities have taken place and clinical trials with three of the Company’s antibodies are expected to start in 2016. A scientific advice meeting with the UK Medicines and Healthcare Products Regulatory Agency (MHRA) was held in preparation for the first clinical study of BI-1206. The study plan presented to the regulator, as well as BioInvent’s data, were well received. Cancer Research UK plans to submit the Clinical Trial Application in April 2016.

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With an increased commitment to the BI-505 program, BioInvent will submit a clinical trial application to the US Food and Drug Administration (FDA) in December 2015.

BioInvent and its partner Oncurios is planning to start a clinical trial with TB-403 in medulloblastoma during early 2016.
BioInvent has established itself as a company with strong clinical programs and a strong position in the immuno-oncology area.

BI-1206
BI-1206 is an antibody that blocks the CD32b protein which is overexpressed in lymphoma (cancer in the lymphatic system). By combining today’s standard of care therapy rituximab (Rituxan/MabThera) with BI-1206, it is possible to achieve a better anti-tumour effect. The planned Phase l/ll clinical study will be sponsored, managed and funded by one of the world’s largest scientific non-profit organisations, Cancer Research UK. This is done under an agreement with BioInvent as part of the Clinical Development Partnerships Scheme, a joint initiative between the Centre For Drug Development and Cancer Research Technology.
In a recent scientific advice meeting with the MHRA, the design of the first clinical study with BI-1206 was discussed. The study will enrol patients with non-Hodgkin lymphoma and chronic lymphatic leukaemia.

Cancer Research UK plans to submit a Clinical Trial Application for the Phase I/II study to the MHRA in April 2016. The lead clinical site at the University of Southampton and at least three other clinical trial sites in the UK will be involved in the trial and aim to be ready to open to recruitment as soon as all necessary regulatory and ethical approvals are in place.

In collaboration with leading academic institutions, BioInvent has started preclinical evaluation of BI-1206 against different sub-types of non-Hodgkin lymphoma using human material from biobanks. The results will provide an important basis for designing the continuing clinical programme.

"The meeting with the UK regulatory agency, MHRA, is an important step forward for BI-1206. We have reached an important milestone in this highly innovative program. We are now in a good position to advance this program further towards market registration for carefully selected patient cohorts with the greatest medical need," says Michael Oredsson, CEO of BioInvent.

BI-505
BI-505 is a human antibody against ICAM-1 developed by BioInvent, which will be clinically tested in cooperation with researchers at Penn Medicine as an immuno-oncological therapy to prevent or delay relapse in patients with multiple myeloma (a form of bone marrow cancer) undergoing stem-cell transplantation. Preclinical data indicates improved activity against myeloma when BI-505 is administered in combination with Velcade or Revlimid. BI-505’s favourable safety profile has been demonstrated in a previous phase I trial. This and the unique mechanism of action, "flagging" remaining myeloma cells for elimination by actively recruited macrophages, as well as the potential to inhibit ICAM-1 dependent survival signals between myeloma cells and tumour stroma, indicate a unique possibility of improving the therapeutic effect of stem-cell transplantation.
Bioinvent plans to submit an application to the FDA in the USA, requesting to start the randomised, controlled phase II study on multiple myeloma patients undergoing autologous stem-cell transplantation, by December 2015 with Penn Medicine as the coordinating site.

The study is expected to start in the first quarter of 2016, which is in line with previous communication.

BioInvent has decided to assume overall responsibility for the study as sponsor of the trial. This will improve control of data and enable expansion of the trial to additional sites, if required.

"By taking on overall responsibility and increasing the number of trial centres for the study with BI-505 we can generate data of the quality required by authorities to enter into discussions regarding a registration procedure based on successful phase II data," says Anna Teige Wickenberg, Vice President Clinical Development, BioInvent.

TB-403
BioInvent and its partner Oncurious are planning to start a new clinical study with the antibody TB-403 against certain rare forms of cancer in the brain, nervous system and connective tissue in children and adolescents. TB-403 has already been evaluated in clinical studies in adults for other cancers and has demonstrated a good safety profile. The project’s new direction is based on new knowledge about the antibody’s mechanism of action. BioInvent has the right to 40 percent of all future revenue from the project.

The study, which is expected to start in early 2016, will be implemented in cooperation with a network of specialist clinics in the USA with good access to the relevant patient cohorts.
The preparations for study start are well underway.

The first safety evaluation part of the study includes patients with medulloblastoma (tumour in the cerebellum), neuroblastoma (tumour in the sympathetic nervous system), Ewings sarcoma (tumour in the connective tissue) and alveolar rhabdomyosarcoma (tumour in the connective tissue), whereas children with medulloblastoma will be included in the efficacy evaluation part of the study.

"Children who suffer from these serious cancers are in great need of more effective treatment and we have therefore prioritised designing a study that should give us the answer as to whether TB-403 is effective in children with medulloblastoma," says Michael Oredsson, CEO of BioInvent.

REGULATORY T-CELLS (TREG)
Regulatory T-cells (Tregs) have a strong ability to inhibit various immune responses. A series of clinical studies show that antibodies targeting CTLA-4 and PD-1 can induce a very long-lasting response in some cancer patients. BioInvent’s F.I.R.S.T technology platform is an excellent tool for identification of both target structures and antibodies in the Treg area.
BioInvent has succeeded in identifying high-affinity antibodies with depleting activity against regulatory T-cells
A first pool of mouse-reactive anti-Treg antibodies, which can be screened in well- established preclinical models to identify novel targets particularly suitable for antibody-mediated Treg depletion, or modulation of Treg immune suppressive activity, have been identified. Target: antibody pairs will be used to evaluate new drug targets and antibody mechanism-of-action in preclinical proof-of-concept tests, paving way for human cross-reactive, or functionally equivalent human lead clinical candidate antibodies. BioInvent recently announced that the Company has received a non-exclusive licence for a special type of antibody format, IgG2B. Preclinical trials with IgG2B antibodies have shown that this antibody type has the potential to more independently activate immune cells e.g. macrophages and T cells to promote anticancer immune responses. When targeted to appropriate receptors, the IgG2b isotype is expected to increase chances of developing new effective drugs in the immune-oncology area.
OX-40

BioInvent is working in cooperation with Cancer Research Technology (CRT) and the University of Southampton in the UK to develop new immunotherapeutic cancer drugs based on antibodies that target OX-40 and 4-1BB, two known co-receptors that help activate T-cells and long-lasting antitumor immune responses.
Antibodies with high affinity, agonistic activity on effector T-cells and the ability to eliminate regulatory T-cells in vitro have been generated.

Preclinical in vivo studies to document proof-of-concept for BioInvent’s antibodies in the OX-40 project will be initiated during the first quarter of 2016.

TUMOUR ASSOCIATED MYELOID CELLS (TAM)
Myeloid cells are essential to our innate immune system, but they can also be "hijacked" by tumours to support growth and cancer spread. In the fourth quarter of 2015, BioInvent worked on preparations to develop function-modulating antibodies against tumour associated myeloid cells (TAM), a type of white blood cell that is recruited by cancer cells to sustain growth and spread, and prevent immune attack. Antibody-mediated "reprogramming" of immune-suppressive tumour-associated myeloid cells into anti-tumor effector cells is therefore a very attractive therapeutic concept and represents an area of research in which BioInvent and its partners are at the cutting edge.

"F.I.R.S.T is a unique platform to identify new antibody-based drugs that more specifically destroy, or transform, cancer-driving immune cells such as Treg and TAM. Preclinical data indicates that antibodies against Treg and TAM can significantly improve the effects of the immunotherapies available today and make it possible to treat cancers where current immunotherapies aren’t working due to a strongly suppressed immune response to the cancer," says Björn Frendéus, Chief Scientific Officer, BioInvent.

Provectus Biopharmaceuticals Reports Immune Mechanism of Action Data for PV-10 Presented at Society for Immunotherapy of Cancer Annual Meeting Authored by Researchers at Moffitt Cancer Center

On December 16, 2015 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus"), reported that it will present at Biotech Showcase 2016 (Press release, Provectus Pharmaceuticals, DEC 16, 2015, http://www.pvct.com/pressrelease.html?article=20151216.1 [SID:1234508585]). The Company will summarize its business operations and discuss PV-10, its novel investigational drug for cancer, and PH-10, its topical investigational drug for dermatology.

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The Company’s presentation is currently set for 3:30 pm Pacific Time on January 13, 2016. The presentation is scheduled to take place on Level 4, the Cyril Magnin Foyer.

The presentation will be available on the Company’s website upon conclusion of the live presentation at the conference.

Aduro Biotech Receives Milestone Payment From Janssen for Acceptance of Investigational New Drug Application for ADU-741 in Prostate Cancer

On December 16, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that it has received a milestone payment from Janssen Biotech, Inc. for the acceptance of an Investigational New Drug (IND) Application by the U.S. Food and Drug Administration for ADU-741, a LADD immunotherapy product candidate for the treatment of prostate cancer (Press release, Aduro BioTech, DEC 16, 2015, View Source [SID:1234508586]).

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Janssen, Aduro’s license partner for ADU-741, plans to initiate a multi-center Phase 1 trial to evaluate the safety and immunogenicity of intravenous administration of ADU-741 by the end of 2015.

"We are extremely pleased with the progress Janssen has made with the development of ADU-741," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "In addition to FDA acceptance of INDs for ADU-741 and ADU-214 in the past two months, we recently received clearance from the FDA for our IND in which we are collaborating with Incyte to begin a clinical trial evaluating the combination of CRS-207 and epacadostat in patients with platinum-resistant ovarian, fallopian and peritoneal cancer. We are thrilled to work with top-notch collaborators like Janssen, Novartis and Incyte, which share the same dedication to the development of novel therapies for patients who need it the most."

In May 2014, Aduro entered into an agreement granting Janssen an exclusive, worldwide license to certain product candidates specifically engineered for the treatment of prostate cancer based on its novel LADD immunotherapy platform. Under the agreement facilitated by Johnson & Johnson Innovation, Aduro received an upfront payment, milestone payments associated with both the submission and the acceptance of the IND, and is eligible to receive future development, regulatory and commercialization milestone payments up to a potential total of $345.5 million. In addition, Aduro is eligible to receive royalties on worldwide net sales upon successful launch and commercialization.

About LADD

LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. The LADD technology has been applied to several novel compounds in clinical and preclinical testing including CRS-207 (pancreatic cancer, mesothelioma and ovarian/fallopian/peritoneal cancer (collaboration with Incyte Corporation to be tested in combination with epacadostat)), ADU-623 (brain cancer), ADU-214 (lung cancer, licensed to Janssen Biotech, Inc.) and ADU-741 (prostate cancer, licensed to Janssen Biotech, Inc.).

Celsion Receives CFDA Approval to Conduct the OPTIMA Study in China

On December 16, 2015 Celsion Corporation (NASDAQ: CLSN) reported that it has received Clinical Trial Application (CTA) approval from the China Food and Drug Administration (CFDA) to conduct the ongoing Phase III OPTIMA Study at clinical sites in China (Press release, Celsion, DEC 16, 2015, View Source [SID:1234508584]).

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The OPTIMA Study is the Company’s global pivotal, double-blind, placebo-controlled trial, evaluating ThermoDox, Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin, in combination with radiofrequency ablation standardized to 45 minutes (sRFA) versus sRFA alone to treat patients with primary liver cancer, also known as hepatocellular carcinoma (HCC). Celsion Corporation is a fully-integrated oncology company focused on the development of a portfolio of innovative cancer treatments, including directed chemotherapies, immunotherapies and RNA- or DNA-based therapies for the treatment of cancer and other difficult-to-treat diseases.

"The OPTIMA Study is the only global Phase III clinical trial being conducted in HCC, and the China market is an important element of our global development strategy for ThermoDox, representing approximately 50% of the 850,000 new cases of primary liver cancer diagnosed each year," noted Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "We believe that this approval by the China FDA represents another important validation of our development program for ThermoDox, which shows the potential for improvement in overall survival in HCC patients. This approval also positions us as a leader in research in a major global market for primary liver cancer," Mr. Tardugno said.

The Phase III OPTIMA Study is expected to enroll up to 550 patients globally, and has been successfully enrolling patients at 50 clinical sites in 12 different countries in North America, Europe and Asia Pacific. The CTA approval will now allow Celsion to enroll patients at up to 25 additional clinical sites in China. With the addition of these Chinese clinical sites, the Company expects to complete enrollment in the OPTIMA Study by the end of 2017. Results from the OPTIMA Study, if successful, will provide the basis for a global registration filing and marketing approval.

The primary endpoint for the OPTIMA Study is overall survival (OS). The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee (iDMC). The design of the OPTIMA Study is supported by a retrospective analysis of a large subgroup of 285 patients in the Company’s previous 701 patient HEAT Study in primary liver cancer. In a subgroup of 285 HEAT Study participants, ThermoDox plus standardized RFA demonstrated a statistically significant improvement in survival of over two years compared to standardized RFA alone. In this large subgroup, the median OS in the ThermoDox plus standardized RFA arm was approximately 80 months, which is considered a curative treatment for HCC.

"There is significant interest in the curative potential for ThermoDox among leading liver cancer experts in China and the world, and we have a number of highly-motivated sites eager to enroll patients in this important study," Mr. Tardugno added. "We are aggressively recruiting patients worldwide, and look forward to building our relationships with these key study sites in China as the trial progresses."

Array BioPharma Announces Phase 3 Binimetinib Trial Meets Primary Endpoint For NRAS-Mutant Melanoma

On December 16, 2015 Array BioPharma (Nasdaq: ARRY) reported top-line results from the ongoing Phase 3 clinical trial of binimetinib in patients with advanced NRAS-mutant melanoma, known as the NEMO trial (Press release, Array BioPharma, DEC 16, 2015, View Source [SID:1234508583]).

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The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine treatment. The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm; hazard ratio (HR) 0.62, [95% CI 0.47-0.80], p < 0.001.

In the trial, binimetinib was generally well-tolerated and the adverse events reported were consistent with previous results in NRAS melanoma patients.

Array plans to submit binimetinib to regulatory authorities for marketing approval in NRAS-mutant melanoma during the first half of 2016. Results from the NEMO trial including progression free survival, overall survival, objective response rate, safety and prespecified subgroup analyses including outcomes in patients who received prior treatment with immunotherapy will be presented at a medical meeting in 2016.

"We are excited to announce positive results from the NEMO trial, which suggest binimetinib has the potential to provide an important new treatment option for patients with advanced NRAS melanoma," said Ron Squarer, Chief Executive Officer, Array BioPharma. "We look forward to discussing the data with the FDA and other regulatory agencies in the near future."

"The presence of an NRAS mutation is a poor prognostic indicator for patients with advanced melanoma," said Keith T. Flaherty, M.D., Associate Professor, Medicine, Harvard Medical School and Director of Developmental Therapeutics, Cancer Center, Massachusetts General Hospital. "I am encouraged the NEMO trial met its primary endpoint and look forward to sharing the full results soon. As the first targeted therapy with positive results in NRAS melanoma, binimetinib will be a welcome addition in this high unmet need population, especially for patients whose disease has progressed following treatment with immunotherapy."

Binimetinib is also being studied in the Phase 3 COLUMBUS trial for patients with BRAF-mutant melanoma and the Phase 3 MILO trial for patients with low grade serous ovarian cancer, as well as in several other earlier stage clinical trials.

About NEMO

The NEMO trial, (NCT01763164), is an international, randomized Phase 3 study in patients with advanced NRAS-mutant melanoma. 402 patients were randomized 2:1 to receive continuous 45 mg BID binimetinib or 1,000 mg/m2 dacarbazine dosed every three weeks. Prior immunotherapy treatment was allowed. The primary endpoint of the study is progression free survival, and overall survival is a key secondary endpoint. Patients underwent radiographic assessment of disease status every six weeks, and assessment of progression was determined by blinded central review. Over 100 sites across North America, Europe, South America, Asia and Australia participated in the study.

About Binimetinib

MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway. Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as non-small cell lung cancer, melanoma, colorectal, ovarian and thyroid cancers. Binimetinib is a small molecule MEK inhibitor which targets key enzymes in this pathway. Binimetinib is being studied in three active Phase 3 trials in advanced cancer patients, including: NRAS-mutant melanoma (NEMO), low-grade serous ovarian cancer (MILO) and BRAF-mutant melanoma (COLUMBUS).

About NRAS Melanoma

Melanoma is the fifth most common cancer among men and the seventh most common cancer among women in the United States, with almost 74,000 new cases and nearly 10,000 deaths from the disease projected in 2015. NRAS mutations occur in approximately 15% to 20% of patients with melanoma, and is known to be a poor prognostic factor. When melanoma is diagnosed early, it is generally a curable disease. However, when it spreads to other parts of the body, it is the deadliest and most aggressive form of skin cancer. Historically, a person with metastatic melanoma typically has a short life expectancy with NRAS melanoma patients living an average of 8.5 months from diagnosis.

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