On May 5, 2016 BIND Therapeutics, Inc. (NASDAQ: BIND), a biotechnology company developing targeted and programmable therapeutics called ACCURINS, reported a research collaboration with Affilogic, a privately held biotechnology company developing affinity proteins called Nanofitins that selectively bind and interact with identified targets (Press release, BIND Therapeutics, MAY 5, 2016, View Source [SID:1234511973]). Schedule your 30 min Free 1stOncology Demo! Under terms of the collaboration, BIND will utilize Nanofitins as targeting ligand components for ACCURINS designed to bind immuno-oncology targets. Upon achievement of proof-of-concept, BIND anticipates expanding the collaboration to develop ACCURINS that incorporate unique combinations of immuno-oncology targeting ligands and new classes of payloads, including oligonucleotides and molecularly targeted therapies.
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"Targeting ligand collaborations are an important part of our strategy to develop innovative medicines and this collaboration provides us with access to targeting ligands that are key modulators of anti-tumor immunity," said Jonathan Yingling, Ph.D., chief scientific officer, BIND Therapeutics. "The modular nature of our platform, including the ability to utilize targeting ligands that elicit a biological response and enhance disease tissue accumulation, will potentially allow us to develop ACCURINS that cause tumor cell death and/or modulate the tumor microenvironment as a way to maximize clinical benefit for patients."
ACCURINS are polymeric nanoparticles that encapsulate and control the release of therapeutic payloads with diverse physical and chemical properties, including highly charged payloads such as oligonucleotides and molecularly targeted therapies that have previously been difficult to formulate in a nanoparticle. Additionally, the surface of ACCURINS can be functionalized with a variety of biologically active ligands, potentially with multiple types of ligands on the same particle. BIND’s collaboration with Affilogic is intended to investigate the use of Nanofitins protein ligands that bind to important immune regulators.
"We are excited about our collaboration with BIND Therapeutics and believe our Nanofitin targeting ligands can play an important role in BIND’s innovative medicine strategy," said Olivier Kitten, chief executive officer, AFFILOGIC. "BIND’s ACCURINS platform has proven very effective at encapsulating and controlling the release kinetics of a wide variety of therapeutic payloads. When combined with our ability to specifically tailor Nanofitins to target important immune-oncology checkpoints, we believe this collaboration could lead to the discovery and development of truly innovative therapeutics."
This early research collaboration is not expected to have a material financial impact on BIND Therapeutics. Additional terms of the collaboration have not been disclosed.
About ACCURINS
ACCURINS are proprietary polymeric nanoparticles that are engineered to target specific cells and tissues in the body at sites of disease. ACCURINS have the potential to achieve therapeutic outcomes not currently possible with conventional treatment modalities. We are developing ACCURINS with three different therapeutic objectives, both through internal research programs and with collaborators:
Innovative medicines: Designing new therapeutic approaches by combining novel targeting methods and new classes of therapeutic payloads.
Enabling potent pathway inhibitors: Enabling greater inhibition of important cellular pathways where that level of inhibition has been unachievable due to off target toxicity.
Differentiated profile with approved drugs: Improving upon safety and efficacy with previously approved chemotherapeutic agents.
ACCURINS can be engineered for multiple therapeutic applications and have the potential to integrate numerous payloads, including highly potent drugs with mechanism-based toxicities that limit therapeutic benefit, DNA, RNA, proteins and immunotherapy agents. This attribute enables ACCURINS to target multiple diseases, including cancer, inflammatory, vascular, and infectious disease.
About Nanofitins
Nanofitins are small affinity proteins that can be easily conjugated to other moieties (small molecule, biologics, nanoparticles) by genetic fusion or standard chemistry (regioselective conjugation). This enables to consider a Nanofitin not only as a neutralizing agent but also as a vector to increase target-specificity and enable cellular uptake. Nanofitins demonstrate many small molecule-like attributes such as a very small size (20 times smaller than a monoclonal antibody), an extreme robustness and a better tissue penetration. Deriving from a naturally hyperstable scaffold, Nanofitins are resistant to temperature and pH, are spontaneously refolding and stable to proteases. Nanofitins are produced by simple, scaleable, GMP- compliant bacterial fermentation at very attractive costs or by chemical synthesis.
Affilogic designs and develops Nanofitins through early-stage collaborations, as well as a proprietary portfolio.
Author: [email protected]
Yissum and BioTheryX Sign Licensing Agreement for the Development of Next-Generation Protein Degradation and Immunomodulatory Treatment for Hematological Cancers
On May 4, 2016 Yissum Research Development Company of the Hebrew University of Jerusalem reported that it had signed an exclusive world-wide licensing and research agreement with BioTheryX, Inc., developer of novel protein degradation and immunomodulatory drugs for cancer and immune dysfunction, for the development and commercialization of drug candidates representing first-in-class therapy for both hematologic and solid malignancies. Financial terms of the license were not disclosed (Press release, , MAY 4, 2016, View Source [SID1234641528]).
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The novel technology was invented by Yinon Ben-Neriah, MD, PhD, Blumenthal Professor of Cancer Research, Lautenberg Center for Immunology, Hebrew University-Hadassah Medical School, with generous support by AMRF (The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation). Dr. Ben-Neriah’s and his team showed that inhibition of the clinically validated enzyme CKI-alpha, induces several tumor suppressor pathways, including a new type of DNA damage response and p53 activation. This provides a novel approach to treat a wide range of cancers, in particular selective types of hematological malignancies.
Prof. Yinon Ben-Neriah has recently received the 2016 Rappaport Prize for excellence in biomedical research, among others, for his ground breaking research on the relationship between chronic inflammation and cancer and the treatment of leukemia.
Based on their complementing expertise, BioTheryX and Yissum have agreed to join forces and focus on the selection and advancement of clinical candidates designed to inhibit CKI-alpha. Initial clinical focus for these candidates will be selective subtypes of myelodysplastic syndrome and acute myeloid leukemia that are not responsive to available cancer therapy.
In preclinical studies of acute leukemia, these clinical candidates showed a far greater therapeutic potential than any previously reported studies. Treatment of genetically-modified leukemic mice modeling poor-prognosis human acute myeloid leukemia, abolished the disease signs in the majority of the animals, without compromising the normal bone marrow, demonstrating that CKI-alpha inhibitors have a large therapeutic window and are unique in their capacity to specifically eliminate leukemia stem cells, including otherwise treatment-resistant stem cells – a strong indication of cancer cure.
Yaacov Michlin, President and Chief Executive Officer, Yissum, commented, "The treatment that was developed in Prof. Ben-Neriah’s lab is very different from other available therapies, both in its mechanism of action and its ability to eliminate leukemic stem cells, and thus in its therapeutic potential. In light of the successful pre-clinical studies, we believe that it offers a significant breakthrough, and we are very pleased to partner with BioTheryX in the development of new drug candidates for potential treatment of a variety of hematological indications. We believe that the combined know-how and research efforts of the teams at BioTheryX and the Hebrew University will facilitate new drug development, leading to significant advancement in the therapy of this class of devastating cancer diseases."
David Stirling, Chief Executive Officer, BioTheryX, commented, "BioTheryX is particularly pleased to partner with the Hebrew University on this important project. Our team, having developed the remarkable IMiD family of drugs while at Celgene, which have improved the quality of life of so many cancer patients and their loved ones, brings a deep wealth of experience to developing novel cancer therapies that modulate protein degradation and the immune system to target cancer causing proteins for destruction. We believe that these unique drug candidates from the Hebrew University will not only bring new treatment modalities to a variety of hematological cancers, but may provide the only option for those patients that relapse and become resistant to currently available therapies."
Anticancer DNA vaccine based on human telomerase reverse transcriptase generates a strong and specific T cell immune response.
Human telomerase reverse transcriptase (hTERT) is overexpressed in more than 85% of human cancers regardless of their cellular origin. As immunological tolerance to hTERT can be overcome not only spontaneously but also by vaccination, it represents a relevant universal tumor associated antigen (TAA). Indeed, hTERT specific cytotoxic T lymphocyte (CTL) precursors are present within the peripheral T-cell repertoire. Consequently, hTERT vaccine represents an attractive candidate for antitumor immunotherapy. Here, an optimized DNA plasmid encoding an inactivated form of hTERT, named INVAC-1, was designed in order to trigger cellular immunity against tumors. Intradermal injection of INVAC-1 followed by electrogene transfer (EGT) in a variety of mouse models elicited broad hTERT specific cellular immune responses including high CD4(+) Th1 effector and memory CD8(+) T‑cells. Furthermore, therapeutic INVAC‑1 immunization in a HLA-A2 spontaneous and aggressive mouse sarcoma model slows tumor growth and increases survival rate of 50% of tumor-bearing mice. These results emphasize that INVAC-1 based immunotherapy represents a relevant cancer vaccine candidate.
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Nordic Nanovector Announces First Patient Enrolled in Arm 3 of Expanded Phase 1/2 Study of Betalutin® in NHL Patients
On May 4, 2016 Nordic Nanovector ASA (OSE: NANO), a biotechnology company focusing on the development of novel targeted therapeutics in haematology and oncology, reported that the first patient has been enrolled into one of the two new arms of its expanded Lymrit 37-01 clinical study with Betalutin (Press release, Nordic Nanovector, MAY 4, 2016, View Source [SID:1234511950]).
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Betalutin is a novel anti-CD37 targeting Antibody Radionuclide Conjugate in development for the treatment of major types of non-Hodgkin’s lymphoma (NHL), including Follicular Lymphoma (FL).
The new arm (Arm 3) is designed to investigate the safety and efficacy of Betalutin in up to 12 patients with relapsed FL pre-dosed with standard anti-CD20 immunotherapy (rituximab) on Day 0, a few hours prior to the administration of Betalutin.
Luigi Costa, Nordic Nanovector CEO, commented: "We are pleased to initiate the first of the two new cohorts in our ongoing clinical study, which represents a significant step forward in Betalutin’s development plan. Data we have seen to date suggest that we can achieve strong clinical efficacy with a regimen that controls haematological side effects. The two new arms are investigating if different pre-dosing regimens will allow the use of higher doses of Betalutin to potentially achieve even higher efficacy than that so far observed, and therefore an even more compelling product profile."
The Lymrit 37-01 study is a Phase 1/2 open label, single injection ascending dose study investigating three dose levels of Betalutin and different dosing regimens in patients with relapsed NHL with the aim of identifying an optimal dose regimen to take into the Phase 2 PARADIGME study, which is expected to start in 2H 2017.
Patient recruitment into the Phase 2 part of Arm 1 (15Mbq/kg plus 50mg/ml unconjugated "cold" HH1 anti-CD37 antibody) is progressing as planned with dose-escalation expected to begin in 2H 2016. Patient screening is also underway for the final arm in the expanded Lymrit 37-01 study (Arm 4), in which escalating doses of Betalutin plus pre-treatment with a higher dose of cold anti-CD37 antibody than in Arm 1 will be evaluated in relapsed FL patients.
A decision to increase the dose of Betalutin to 17.5 MBq/kg in Arm 1 can be made based on the evaluation of the safety and efficacy data observed in the 15 patients treated with 15 MBq/kg. A decision to increase the dose of Betalutin to 17.5 MBq/kg or 20 MBq/kg in one or the other of Arms 3 and 4 can be made based on the evaluation of the safety and efficacy data observed in the first three patients of both cohorts.
Data and analysis recently published at the American Association of Cancer Research annual meeting (16-20 April) confirmed that Betalutin was generally well tolerated and showed a 63.2% Overall Response Rate (ORR) and a 31.6% Complete Response (CR) in evaluable patients. Clinical responses observed were sustained, with Duration of Response exceeding 12 months in most responders in the 15 MBq/kg group who have been followed up for at least 12 months.
Exelixis Announces First Quarter 2016 Financial Results and Provides Corporate Update
On May 4, 2016 Exelixis, Inc. (Nasdaq: EXEL) reported financial results for the first quarter of 2016 and provided an update on progress toward delivering upon its key 2016 corporate objectives and clinical development milestones (Press release, Exelixis, MAY 4, 2016, View Source;p=RssLanding&cat=news&id=2165093 [SID:1234511947]).
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Corporate Updates and Key Priorities for 2016
On April 25, 2016, the U.S. Food and Drug Administration (FDA) approved CABOMETYX (cabozantinib) tablets as a treatment for patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. With approval granted, Exelixis is highly focused on the U.S. commercial launch for CABOMETYX. CABOMETYX was shipped to wholesalers and pharmacies within three days of approval, with the first prescription filled on April 28, 2016. The European Medicines Agency (EMA) is reviewing the company’s Marketing Authorization Application (MAA) for cabozantinib for advanced RCC; assuming approval, the product would be marketed in the EU by the company’s corporate partner, Ipsen Pharma SAS (Ipsen).
Exelixis continues to work with its partner Genentech, a member of the Roche Group, to co-promote COTELLIC (cobimetinib) in the United States as a treatment for patients with BRAF V600E or V600K mutation-positive advanced melanoma, in combination with vemurafenib, also known as Zelboraf. COTELLIC is also approved in multiple other territories including the EU and Canada.
Corporate Highlights
Exclusive Licensing Agreement with Ipsen for Cabozantinib in Regions Outside the United States, Canada and Japan. On February 29, 2016, Exelixis announced an exclusive licensing agreement with Ipsen for the commercialization and further development of cabozantinib for its current and potential future indications, including COMETRIQ (cabozantinib) capsules, outside the United States, Canada and Japan. Pursuant to the parties’ agreement, Exelixis received an upfront payment from Ipsen of $200.0 million in the first quarter of 2016. The company is also eligible to receive regulatory milestones, including $60.0 million upon the approval of cabozantinib in Europe for advanced RCC and $50.0 million upon the filing and approval of cabozantinib in Europe for advanced hepatocellular carcinoma (HCC), as well as additional development and regulatory milestones for potential further indications. The agreement includes up to $545.0 million of potential commercial milestones and provides for Exelixis to receive tiered royalties up to 26% on Ipsen’s net sales of cabozantinib in its territories. Exelixis and Ipsen have agreed to collaborate on the global development of cabozantinib for current and potential future indications as well.
Cabozantinib Highlights
FDA Approval of CABOMETYX, the Third Approved Medicine to Have Been Discovered by Exelixis. On April 25, 2016, the U.S. FDA approved CABOMETYX for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy. CABOMETYX is the first therapy to demonstrate robust and clinically meaningful improvements in all three key efficacy parameters – overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) – in a phase 3 trial (METEOR) for patients with advanced RCC.
The CABOMETYX label includes data from the second interim analysis of the METEOR trial’s OS secondary endpoint. In February 2016, Exelixis announced that CABOMETYX demonstrated a highly statistically significant and clinically meaningful improvement in OS as compared to everolimus. These results have been accepted as an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting, June 3-7, in Chicago, and will be presented in detail on Sunday, June 5, during the Oral Abstract Session: Genitourinary (Nonprostate) Cancer, 10:12 – 10:24 a.m.
Progress on EU Regulatory Filing for Cabozantinib in Advanced RCC. In January 2016, Exelixis submitted, and the EMA subsequently validated, the company’s regulatory application for cabozantinib as a treatment for patients with advanced RCC who have received one prior therapy. In validating the MAA, the EMA granted accelerated assessment, making the application eligible for a shortened 150-day review excluding clock-stops when information is requested from Exelixis. Exelixis intends to transfer the MAA to Ipsen later this year.
Continued Enrollment in CELESTIAL; Data Anticipated in 2017. Exelixis continues to make progress with enrollment of CELESTIAL, the phase 3 pivotal trial comparing cabozantinib to placebo in patients with advanced HCC who have previously been treated with sorafenib. Initiated in September 2013, the trial is designed to enroll 760 patients at approximately 200 sites. Patients are being randomized 2:1 to receive 60 mg of cabozantinib daily or placebo. The primary endpoint for CELESTIAL is OS, and the secondary endpoints include PFS and ORR. Exelixis continues to anticipate top-line results from CELESTIAL in 2017. At this time, there is no approved treatment for HCC patients who progress following sorafenib treatment, the current standard of care.
Broad Cabozantinib Development Program Updates. While Exelixis pursues cabozantinib’s late-stage development in advanced RCC and advanced HCC, earlier-stage investigation of the compound continues through the company’s collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP), and its ongoing Investigator-Sponsored Trial (IST) program. Through these two programs, there are more than 45 ongoing or planned studies including trials in advanced RCC, bladder cancer, colorectal cancer, non-small cell lung cancer, and endometrial cancer.
Cabozantinib, Cobimetinib and XL888 Data Presentations at ASCO (Free ASCO Whitepaper) 2016. Exelixis-discovered compounds will be the subject of 18 presentations at the meeting. In addition to the OS results from the METEOR study in advanced RCC, there will be a poster presentation from the same trial on outcomes based on prior therapy. Additional presentations will highlight results from early and mid-stage trials of cabozantinib in other disease settings, including metastatic colorectal cancer, endometrial cancer and metastatic urothelial carcinomas. Cobimetinib data will include updates on combination trials of the compound in metastatic melanoma, triple-negative breast cancer, and colorectal cancer. Exelixis will also host an investor/analyst briefing at the meeting on Sunday, June 5, 2016; see the Investors & Media section of www.exelixis.com for more details when available.
Cobimetinib Highlights
Additional Regulatory Approvals for COTELLIC. In April and May 2016, Australia’s Therapeutic Goods Administration and Brazil’s ANVISA, respectively, approved COTELLIC for use in combination with Zelboraf for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation. As previously announced, in February 2016 Health Canada approved COTELLIC in combination with Zelboraf for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation.
2016 Financial Guidance
The Company is maintaining its guidance that operating expenses for the full year 2016 will be between $240 million and $270 million, including approximately $30 million of non-cash items primarily related to stock-based compensation expense.
"The first quarter of 2016, and the time period following it, was marked by important advances not only for our company, but for the patients we serve," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "Most notably, just a little over a week ago we announced that the FDA approved CABOMETYX for advanced RCC, a major milestone for the company. We are especially pleased that the label includes the robust overall survival data from the METEOR trial. CABOMETYX is now the first and only therapy to have demonstrated improvements in the three key efficacy parameters in a phase 3 trial of advanced renal cell carcinoma, one of the most common forms of cancer for men and women in the United States. We are moving quickly to introduce this new and important medicine to the medical community, with our experienced U.S. commercial team already in the field and meeting with healthcare providers. With our partner Ipsen, we are also well positioned to advance the process of seeking approval and potentially commercializing CABOMETYX in markets beyond the U.S., Canada and Japan."
First Quarter 2016 Financial Results
Net revenues for the quarter ended March 31, 2016 were $15.4 million, compared to $9.4 million for the comparable period in 2015. Net revenues for the first quarter of 2016 consisted of $9.1 million of net product revenue related to the sale of COMETRIQ, $5.0 million of contract revenues for a milestone earned from Merck in the first quarter of 2016 related to their worldwide license of our PI3K-delta program and $1.2 million of license revenues recognized from the upfront payment we received from Ipsen under our collaboration and license agreement.
Research and development expenses for the quarter ended March 31, 2016 were $28.9 million, compared to $22.3 million for the comparable period in 2015. The increase was primarily related to an increase in stock-based compensation expense for performance-based stock-options and an annual bonus to our employees in the form of fully-vested restricted stock units, an increase in personnel related expenses resulting from an increase in headcount and an increase in consulting and outside services for medical affairs and drug safety.
Selling, general and administrative expenses for the quarter ended March 31, 2016 were $34.9 million, compared to $9.5 million for the comparable period in 2015. The increase was primarily related to an increase in personnel related expenses resulting from an increase in headcount, predominantly connected to the expansion of our U.S. sales force, higher marketing expenses which includes a portion of commercialization expenses from COTELLIC under our collaboration agreement with Genentech, consulting and outside services expenses which includes an accrual for the estimated termination fee due to Sobi, and stock-based compensation expense for performance-based stock-options and an annual bonus to our employees in the form of fully-vested restricted stock units.
Other income (expense), net for the quarter ended March 31, 2016 was a net expense of ($12.2) million compared to ($12.4) million for the comparable period in 2015. The net expense is comprised primarily of interest expense which includes $7.2 million of non-cash expense related to the accretion of the discounts on both the 4.25% Convertible Senior Subordinated Notes due 2019 and the Company’s indebtedness under our Secured Convertible Notes due June 2018 held by entities associated with Deerfield for the quarter ended March 31, 2016, as compared to $7.7 million for the comparable period in 2015.
Net loss for the quarter ended March 31, 2016 was ($61.3) million, or ($0.27) per share, basic, compared to ($35.2) million, or ($0.18) per share, basic, for the comparable period in 2015. The increased net loss for the quarter was primarily due to increases in selling, general and administrative expenses and research and development expenses, partially offset by an increase in net revenues.
Cash and cash equivalents, short- and long-term investments and long-term restricted cash and investments totaled $407.6 million at March 31, 2016, which increased from $253.3 million at December 31, 2015 as a result of the $200.0 million upfront payment we received from Ipsen in connection with our February 29, 2016 licensing agreement.
Basis of Presentation
Exelixis adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31st. For convenience, references in this press release as of and for the fiscal periods ended April 1, 2016, January 1, 2016 and March 28, 2015 are indicated as being as of and for the periods ended March 31, 2016, December 31, 2015 and March 31, 2015, respectively.