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FDA Grants Priority Review for Venetoclax New Drug Application

On January 12, 2016 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) and granted Priority Review for venetoclax for the treatment of people with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, including those with 17p deletion (Press release, Genentech, JAN 12, 2016, View Source [SID:1234508776]).

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Venetoclax is a small molecule inhibitor of the BCL-2 protein being developed in partnership with AbbVie, and was granted Breakthrough Therapy Designation by the FDA in April 2015 for the treatment of people with previously treated (relapsed or refractory) CLL with 17p deletion.

"Venetoclax is a potential new way to treat this difficult type of chronic lymphocytic leukemia," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We look forward to working with AbbVie and health authorities to bring this first-of-its-kind medicine to people who need more options."

A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. The NDA for venetoclax is based in part on data from the pivotal Phase II M13-982 study. A Marketing Authorization Application (MAA) has also been validated by the European Medicines Agency (EMA).

About Study M13-982
The NDA for venetoclax is based in part on data from the pivotal Phase II M13-982 study. M13-982 (NCT01889186) is a Phase II, open-label, single arm, multicenter study evaluating the efficacy and safety of venetoclax in patients with relapsed, refractory or previously untreated chronic lymphocytic leukemia (CLL) with 17p deletion. The study included 107 patients with relapsed or refractory disease, and all but one had 17p deletion. Additionally, about 50 patients with relapsed, refractory or previously untreated disease have been enrolled in the safety expansion cohort. The primary endpoint of the study is overall response rate (ORR) as determined by an independent review committee (IRC), and secondary endpoints include complete response (CR), partial response (PR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The level of minimal residual disease (MRD) in peripheral blood and/or bone marrow was assessed in a subset of patients.

Results from the study were recently presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting showing:

The study met its primary endpoint, with an ORR of 79.4 percent among the 107 patients with relapsed or refractory disease receiving venetoclax, as assessed by IRC. In addition, 7.5 percent of patients achieved a complete response with or without complete recovery of blood counts in the bone marrow (CR/CRi).
Forty-five patients had an assessment for MRD in the blood. Of these, 18 patients achieved MRD-negativity, meaning no cancer could be detected using a specific test. Ten of these 18 patients also had bone marrow assessments and six were MRD-negative.
At one year, 84.7 percent of all responses and 94.4 percent of MRD-negative responses were maintained. The one-year PFS and OS rates were 72 percent and 86.7 percent, respectively.
The most common serious adverse events were fever (7 percent), low red blood cell count as a result of immune response (7 percent), pneumonia (6 percent) and low white blood cell count with fever (5 percent). The most common Grade 3-4 adverse events were low white blood cell count (40 percent), low red blood cell count (18 percent) and low platelet count (15 percent). Grade 3 or higher infection occurred in 20 percent of patients. Laboratory tumor lysis syndrome was reported in five patients; none had clinical consequences.
About Venetoclax (RG7601, GDC-0199/ABT-199)
Venetoclax is an investigational small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). It is believed that blocking BCL-2 may restore the signaling system that tells cells, including cancer cells, to self-destruct. The BCL-2 protein is linked to the development of resistance in certain blood cancers and is expressed in chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). In collaboration with AbbVie, venetoclax is being evaluated in a robust development program as a single agent or in combination with other medicines. There are ongoing Phase II and III studies for venetoclax in CLL, and Phase I and II studies are also ongoing in several other blood cancers, including indolent NHL, diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML) and multiple myeloma (MM).

About Chronic Lymphocytic Leukemia (CLL)
CLL is one of the most common forms of blood cancer, and each year there are an estimated 5,000 deaths from CLL in the United States. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.
In certain cases of CLL, a part of chromosome 17 is lost and along with it an important gene that controls apoptosis (programmed cell death) called p53. The 17p deletion is found in 3 to 10 percent of previously untreated cases and approximately 30 to 50 percent of relapsed or refractory cases.

Surface Oncology Announces Global Strategic Collaboration to Advance Next‐Generation Immunotherapies

On January 11, 2016 Surface Oncology (Surface), a leader in the development of next‐generation cancer immunotherapies, reported that it has entered into a broad strategic collaboration with Novartis to develop immunotherapeutics targeting the tumor microenvironment and the interface of innate and adaptive immunity (Press release, Surface Oncology, JAN 11, 2016, View Source [SID1234527366]). "This strategic collaboration reflects our shared commitment to innovation in cancer immunotherapy beyond checkpoint inhibitors," said Detlev Biniszkiewicz, CEO of Surface. Biniszkiewicz added "It fuels our pipeline, provides the option to co‐develop and cocommercialize half of the partnership programs, and allows us to further build value as an independent company as we also pursue new programs outside of the collaboration." Under the terms of the agreement, Surface is eligible to receive up to $170M in upfront, equity, and near‐term milestone payments. Novartis will gain exclusive access to Surface’s current pipeline of novel cancer immunotherapies, including an exclusive worldwide license to its leading program and options to license up to three additional programs from the existing portfolio, exercisable at IND. Surface is eligible to receive clinical and commercial milestones and up to double‐digit royalties on product sales. Surface also has the option to retain U.S. development and commercialization rights for at least half of the collaboration’s programs. Mark C. Fishman, M.D., President of the Novartis Institutes for BioMedical Research, commented, "We are very excited to enter into this collaboration with Surface. This alliance is another building block in our strategy to develop a portfolio of programs that we believe will
lead the next wave of immuno‐oncology medicines."

Advanced Accelerator Applications Signs Exclusive License Agreement With Johns Hopkins University to Develop PSMA Receptor Ligand in Prostate Cancer

On January 11, 2016 Advanced Accelerator Applications S.A. (NASDAQ:AAAP) ("AAA" or "the Company"), an international specialist in molecular nuclear medicine, reported an exclusive license agreement with Johns Hopkins University in Baltimore, Maryland to develop and market PSMA-SR6, a receptor ligand of Prostate-Specific Membrane Antigen (PSMA) for clinical therapeutic and diagnostic purposes (Press release, Johns Hopkins University, JAN 11, 2016, View Source [SID1234524452]). AAA will focus on developing this treatment and its companion diagnostic for prostate cancer through novel molecular nuclear medicine techniques similar to those implemented for the development of Lutathera and Somakit. Prostate cancer affects nearly 1 in 7 men during their lifetime worldwide.

The terms of the agreement include payment to Johns Hopkins of an upfront licensing fee, as well as certain milestone and royalty payments.

"This licensing agreement is the first step toward broadening our development pipeline by leveraging a formula that we have already successfully applied to develop our lead therapeutic and diagnostic candidates Lutathera and Somakit. We plan to radiolabel PSMA-SR6, to develop a 177Lu-PSMA-SR6 to treat and monitor prostate cancer and a 68Ga-PSMA-SR6, which will help to diagnose and stage disease. The PSMA expression pathway has been widely investigated with labelled antibodies, but we believe that a small molecule, with very high specificity and rapid uptake into tumors and clearance from non-targeted organs could be the ideal candidate for a full theragnostic approach. We are very pleased to partner with the Johns Hopkins University as they have been pioneering and leading this new field for many years," says Stefano Buono, Chief Executive Officer of AAA.

"Our license agreement with AAA extends Johns Hopkins University’s research leadership in PSMA to benefit patients," says Neil Veloso, Executive Director of Johns Hopkins Technology Ventures. "We are very pleased that AAA has selected PSMA-SR6 for full development for commercial applications in an area of significant patient need."

AAA is planning to support a proof-of-concept study in humans that may start in 2016 for both diagnostic and therapeutic applications of PSMA-SR6.

PSMA-SR6 is a unique second-generation selective prostate cancer PSMA receptor ligand developed by Dr Martin Pomper at Johns Hopkins University. PSMA-SR6 has a unique structure and is selective for PSMA expressed on prostate cancer tumor cells. It belongs to a new class of PSMA receptor ligands with high potential as diagnostic and therapeutic markers for prostate cancer. Studies have consistently demonstrated PSMA expression in all types of prostate tissue and an increased PSMA expression in cancer tissue.

Tensha Therapeutics To Be Acquired By Roche

On January 11, 2016 Tensha Therapeutics, a privately-held company based in Cambridge, MA, reported it will be acquired by Roche (Press release, Tensha Therapeutics, JAN 11, 2016, View Source [SID1234518479]). Founded by James E. Bradner, MD, of the Dana-Farber Cancer Institute, and managed and funded by HealthCare Ventures, Tensha has developed a pioneering epigenetic technology that disrupts bromodomain and extra terminal domain (BET) proteins in order to develop potential treatments for cancer. The lead product, TEN-010, is a small molecule BET inhibitor that is currently in two Phase 1b clinical trials for the treatment of patients with cancer.

"BET inhibitors function as targeted therapy in rare cancers with BET gene rearrangements (NUT midline carcinoma), and in common cancers as a means of inhibiting the function of the master growth control genes, such as MYC."
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Under the terms of the agreement, Tensha’s shareholders will receive an upfront cash payment of $115 million, plus additional contingent payments of up to $420 million based on the achievement of certain predetermined clinical and regulatory milestones. The transaction is subject to customary closing conditions and anticipated to close in the first quarter of 2016.

"BET proteins are a highly promising class of therapeutic targets in cancer," said James Bradner, MD, Founder of Tensha, Associate Professor at Harvard Medical School, and Investigator at the Dana-Farber Cancer Institute. "BET inhibitors function as targeted therapy in rare cancers with BET gene rearrangements (NUT midline carcinoma), and in common cancers as a means of inhibiting the function of the master growth control genes, such as MYC."

"We selected TEN-010 as a highly selective, potent BET inhibitor, and we moved rapidly and strategically to advance its development," said Steven Landau, MD, Chief Medical Officer of Tensha and Director of Clinical and Scientific Analysis for HealthCare Ventures. "Our initial clinical data demonstrating the potential of TEN-010 in patients with NUT midline carcinoma was presented at the AACR (Free AACR Whitepaper)/NCI/EORTC conference in November."

"We are very excited about this acquisition, as it moves TEN-010 into the pipeline of a world leader in the development of novel cancer therapeutics. With leadership in solid and hematological tumors and deep understanding of BET biology, Roche is the ideal company to explore the broad clinical potential of TEN-010," said Douglas E. Onsi, Chief Executive Officer of Tensha and Managing Director of HealthCare Ventures. "We appreciate the work of the Bradner lab, the Tensha and HealthCare Ventures employees, and the clinical teams at our trial sites for their important roles in bringing TEN-010 to studies in patients."

About BET Proteins

Bromodomain and extra terminal domain (BET) proteins are central mediators of gene control and cellular memory. In cancer, BET proteins activate growth and survival genes. Further, they contribute to cancer cell memory by binding to the genome as molecular bookmarks. Tensha’s Founder, James Bradner, MD, Associate Professor at the Dana-Farber Cancer Institute and Harvard Medical School, was the first to recognize the broad potential of BET inhibitors as anti-cancer agents. The Bradner lab first reported BET inhibitors in 2010 in Nature magazine, and established the potential of BET inhibitors in solid tumors and blood cancers. With chemist Jun Qi, Bradner thereafter invented TEN-010, a best-in-class BET inhibitor, for clinical development. BET inhibitors function as targeted therapy in rare cancers with BET gene rearrangements (NUT midline carcinoma), and in common cancers as a means of inhibiting the function of the master growth control genes, such as MYC. BET inhibition represents a new paradigm of targeting cellular memory, or epigenetics, in cancer, inflammation, and fibrosis.

AstraZeneca and Moderna Therapeutics Announce New Collaboration to Co-Develop and Co-Commercialize Immuno-Oncology mRNA Therapeutics

On January 11, 2016 AstraZeneca, along with its global biologics research and development arm, MedImmune, and Moderna Therapeutics reported a new collaboration to discover, co-develop and co-commercialize messenger RNA (mRNA) therapeutic candidates for the treatment of a range of cancers (Press release, Moderna Therapeutics, JAN 11, 2016, View Source [SID1234517365]). The collaboration is in addition to the agreement announced by the companies in 2013 to develop mRNA Therapeutics for the treatment of cardiovascular, metabolic and renal diseases as well as selected targets in oncology.

The collaboration will combine MedImmune’s protein engineering and cancer biology expertise with Moderna’s mRNA platform. mRNA-based therapies are an innovative treatment approach that enables the body to produce therapeutic protein in vivo, opening up new treatment options for a wide range of diseases that cannot be addressed today using existing technologies.

Under the terms of the new agreement, AstraZeneca and Moderna, a pioneer of mRNA Therapeutics, have agreed to collaborate on two specific immuno-oncology programs, based on promising pre-clinical data, including pharmacology in tumor models. Moderna will fund and be responsible for discovery and preclinical development of product candidates, with the aim of delivering one Investigational New Drug (IND) application-ready molecule for each of the two programs. Moderna’s efforts will be led by its oncology-focused venture, Onkaido. AstraZeneca will be responsible for early clinical development, led by MedImmune, and Moderna and AstraZeneca will share the costs of late-stage clinical development. The two companies will co-commercialize resulting products in the US under a 50:50 profit sharing arrangement. AstraZeneca will lead ex-US commercialization efforts, with Moderna receiving tiered royalties up to substantial double digits on ex-US sales.

Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "We’re pleased to be expanding our relationship with Moderna with this new collaboration, to advance the potential of pioneering messenger RNA technology in developing game-changing new treatments for cancer patients."

"Since our companies’ original strategic agreement in March 2013, Moderna’s relationship with AstraZeneca has been very fruitful. This new agreement with AstraZeneca demonstrates the effectiveness of our existing relationship and the power of our mRNA technology," said Stéphane Bancel, Chief Executive Officer of Moderna. "We’re gratified to deepen our relationship with AstraZeneca and MedImmune with this major initiative, and we look forward to getting underway immediately with our new joint immuno-oncology programs."

Under the companies’ original strategic agreement, AstraZeneca holds exclusive access to select any target of its choice in cardiometabolic diseases, as well as select targets in oncology, over a period of up to five years for subsequent development in mRNA. Several projects are progressing towards clinical development under the arrangement, and a first-in-human study is expected to commence in late 2016.

With its novel technology to enable mRNA as a drug, Moderna is building a fully scaled drug discovery and development platform centered on the rapid and low-cost design, delivery and production of mRNA drug candidates. Moderna is also advancing an innovative business model built on the decentralization of drug development activities. With an ecosystem of in-house concept development, ventures focused on therapeutic areas and a cluster of major pharma and biotech partners, Moderna is enabling more than 90 discovery and preclinical programs today across oncology, infectious diseases, rare diseases and cardiovascular diseases. Moderna’s pipeline also covers a broad expanse of novel drug modalities, each representing a distinct approach to using the company’s novel mRNA expression platform to encode proteins that achieve a therapeutic benefit.