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SQZ BIOTECH ANNOUNCES PARTNERSHIP TO FIGHT CANCER WITH NOVEL CELL ENGINEERING TECHNOLOGY

On December 7, 2015 SQZ Biotech (SQZ) reported a partnership with Roche to develop a cell therapy platform that would empower a patient’s own immune cells to fight a broad range of cancers. The deal leverages SQZ’s pioneering technology to engineer B cells as a therapeutic platform for oncology – a novel approach with the potential to overcome many of the shortcomings of current cell-based therapies (Press release, SQZ Biotech, DEC 7, 2015, View Source [SID:1234508485].

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The agreement provides for over $500M in upfront and potential clinical, regulatory and sales milestone-based payments for advancement of all products across all planned indications, in addition to royalties on potential future products.

"The therapeutic potential of SQZ technology builds on our ground breaking ability to engineer cell function through intracellular delivery – a long standing challenge in immunology," said Dr. Armon Sharei, Founder and Chief Executive Officer of SQZ. "In collaboration with the renowned team at Roche, we seek to engineer a patient’s own immune system to target tumors more effectively and bring hope to people suffering from cancer."

The proposed therapy involves using SQZ technology to introduce proteins into a patient’s Bcells which will then help activate killer T-cells to attack the cancer. The ability to engineer such a response is fundamentally dependent on effective delivery of tumor-associated proteins, or antigens, into the patient’s B cells. This delivery process is uniquely enabled by SQZ’s technology and harnesses the power of the patient’s own immune system to fight tumors more effectively across a broad range of cancer types.

Executive Chair of the SQZ Board Amy Schulman noted, "We are excited about this partnership because it capitalizes on the unique scientific platform that SQZ provides to engineer immune cell function. This is an important first step towards a new generation of cell based therapies." SQZ Biotech also announced the addition of two new board members: Dr. Mark Murcko, a key contributor to seven marketed drugs and the former CTO and SAB Chair of Vertex, and Garry Nicholson, President and Chief Executive Officer of XTuit Pharmaceuticals, Inc., a biopharmaceutical company developing novel micro-environment activated therapeutics and prior head of Pfizer’s global cancer business. Professor Arlene Sharpe, leader of the Dana- Farber Cancer Immunology Program and co-inventor of the first anti-PD-1 therapy, will join the

SQZ Scientific Advisory Board which already comprises a number of thought leaders including professors: Darrell Irvine (MIT), Tyler Jacks (MIT), Christopher Love (MIT), and Ulrich von Andrian (Harvard).

"We welcome the outstanding minds that are joining our efforts," added Schulman. "Mark, Garry and Arlene bring a host of scientific and business experience that will help us with a very exciting period of development and commercialization. We are also proud of Armon, an exceptional young leader, and the entire SQZ team as they work together on what promises to be an exciting journey."

About SQZ Biotech
SQZ Biotechnologies was spun out of MIT based on a scientific breakthrough by Dr. Armon Sharei, Prof. Klavs Jensen and Prof. Robert Langer. The company is based in Boston, MA and backed by Polaris Venture Partners and 20/20 Healthcare Partners. Applications for the SQZ platform beyond oncology are numerous, with the company planning to pursue powerful immune engineering approaches in a number of indications. SQZ maintains the exclusive worldwide license from the Massachusetts Institute of Technology for CellSqueeze for any application.

About Dr. Mark Murcko
Dr. Murcko brings over 25 years of leadership experience in the biomedical field. He has been a key contributor to seven marketed drugs in the fields of glaucoma, HIV, HCV, and Cystic Fibrosis. Dr. Murcko is a lecturer in the Bioengineering department at MIT, serves on numerous biotech boards and is the former CTO and SAB Chair of Vertex Pharmaceuticals.

About Garry Nicholson
Mr. Nicholson brings 20 years of experience in oncology drug development and commercialization. He most recently served as President, Pfizer Oncology, from May 2008 until March 2015. As the first leader of Pfizer’s global, dedicated oncology business, Mr. Nicholson had direct responsibility for business strategy and operations, including the oncology sales and marketing organizations globally, clinical development for both early and late stage pipeline candidates, and for licensing and acquisitions.

About Professor Arlene Sharpe
Dr. Sharpe is the George Fabyan Professor of Comparative Pathology at Harvard Medical School, Head of the Division of Immunology in the Department of Microbiology and Immunobiology, and Co-Director of the Harvard Institute of Translational lmmunology at Harvard Medical School, and a member of the Department of Pathology at Brigham and Women’s Hospital. Dr. Sharpe earned her A. B from Harvard University and her M.D. and Ph.D. degrees from Harvard Medical School. She currently serves as the Vice President of the American Association of Immunologists.
Dr. Sharpe’s laboratory investigates T cell costimulation and its immunoregulatory functions. Her laboratory studies the roles of T cell costimulatory and coinhibitory pathways in regulating immune responses needed for the induction and maintenance of T cell tolerance and effective antimicrobial and antitumor immunity. Dr. Sharpe has published over 300 papers and was listed by Thomas Reuters as one of the most Highly Cited Researchers (top 1%) in 2014 and 2015. She was a recipient of the William B. Coley Award for Distinguished Research in Tumor immunology in 2014 for her contributions to the discovery of PD-1 pathway.

Novartis highlights new CTL019 Phase II data demonstrating 93% complete remission in pediatric patients with r/r ALL

On December 7, 2015 Novartis reported that the latest findings from an ongoing Phase II study of CTL019, an investigational chimeric antigen receptor T cell (CART) therapy, further support its potential in the treatment of children and young adults with relapsed/refractory acute lymphoblastic leukemia (r/r ALL) (Press release, Novartis, DEC 7, 2015, View Source [SID:1234508479]).

The study found that 55 of 59 patients (93%) experienced complete remissions (CR) with CTL019. These results will be presented in an oral session at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Monday, December 7 (Abstract #681, 3:15 p.m.)[1].

In the study, median follow up was 12 months, overall survival was 79% at 12 months (95% CI, 69-91%) and relapse-free survival was 76% at six months (95% CI, 65-89%) and 55% at 12 months (95% CI, 42-73%). Results found that 18 patients had ongoing CR after 12 months of therapy[1].

"This clinical trial of CTL019 is the largest study of a CART therapy in pediatric patients with relapsed or refractory acute lymphoblastic leukemia, and it is helping us better understand the therapy’s potential to achieve durable responses in this patient population," said lead investigator Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania (Penn), and director of Translational Research in the Center for Childhood Cancer Research at the Children’s Hospital of Philadelphia (CHOP). The ongoing study of CTL019 in pediatric patients with r/r ALL is being led by Dr. Grupp at CHOP and is sponsored by Penn.

Additionally, 52 of 59 (88%) patients developed Grade 1-4 cytokine release syndrome (CRS). CRS may occur after CTL019 infusion when the engineered cells become activated and multiply in the patient’s body. During CRS, patients typically experience varying degrees of flu-like symptoms with high fevers, nausea, muscle pain, and in some cases, low blood pressure and breathing difficulties. Treatment for CRS was required for hemodynamic or respiratory instability in 27% of patients and was reversed in all cases with an IL-6 receptor antagonist[1].

"We have observed pediatric patients in this study achieve complete remissions with CTL019 treatment, in many cases without stem cell transplantation, which underscores the potential for CTL019 to fill an unmet medical need," said Usman Azam, MD, Global Head, Cell & Gene Therapies Unit, Novartis Pharmaceuticals. "These new longer-term data add to the growing understanding of CTL019 for patients with relapsed or refractory acute lymphoblastic leukemia who run out of treatment options."

Novartis recently expanded its own global multisite Phase II clinical trial of CTL019 in pediatric r/r ALL with the opening of study sites in Europe, Canada and Australia. A list of participating trial centers is available at View Source (link is external).

Novartis and Penn have an exclusive global collaboration to research, develop and commercialize CART therapies for the investigational treatment of cancers. In July 2014, the FDA designated CTL019 as a Breakthrough Therapy for the treatment of pediatric and adult patients with r/r ALL under the Penn Investigational New Drug application (IND). Breakthrough Therapy designation is intended to expedite the development and review of drugs that treat serious or life-threatening conditions if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint. Novartis holds the worldwide rights to CARs developed through the collaboration with Penn for all cancer indications, including the lead program, CTL019.

Additional key CART data presented at ASH (Free ASH Whitepaper) include:

Findings from a study on treatment with CTL019 in children with r/r ALL that face additional central nervous system (CNS) relapse complications (Abstract #3769, December 7, 6-8 p.m.)[2]

Data on characterization and accurate early prediction of CRS in r/r ALL patients treated with CTL019 (Abstract #1334, December 5, 5:30 p.m.)[3]

Preliminary efficacy and safety data on humanized CTL119 in children with r/r ALL (Abstract #683, December 7, 3:45 p.m.)[4]
Preclinical data from a study on CART123 to mitigate toxicity in acute myeloid leukemia (Abstract #565, December 7, 10:30 a.m.)[5]

Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of uncertainty of clinical trials, there is no guarantee that CTL019 will ever be commercially available anywhere in the world.

Juno’s Investigational CAR T Cell Product Candidates JCAR015 and JCAR014 Demonstrate Encouraging Clinical Responses in Patients with B-cell Cancers

On December 7, 2015 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported, in partnership with its collaborators, that clinical data from separate trials for chimeric antigen receptor (CAR) T cell product candidates, JCAR015 and JCAR014, demonstrated encouraging clinical responses in patients with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) (Press release, Juno, DEC 7, 2015, View Source [SID:1234508478]).

JCAR015 and JCAR014 results will be presented in oral and poster presentations, respectively, today at the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando.

"We are encouraged by the continued positive results of JCAR015 in adult patients with r/r ALL. We look forward to advancing this product candidate in its ongoing pivotal Phase II trial, with the goal of potentially making it broadly available to patients," said Mark Frohlich, M.D., Executive Vice President, Development and Portfolio Strategy. "The JCAR014 data presented show the addition of fludarabine to cyclophosphamide-based lymphodepletion improves CAR T cell expansion, persistence, and disease-free survival in r/r B-cell adult ALL patients treated with a defined cell product. The continued translational insights from this ongoing trial also demonstrate the importance of depth of response in order to maintain a durable response."

In an oral presentation on Monday, December 7, 2015, Jae H. Park, M.D. of Memorial Sloan Kettering Cancer Center will present, "Implications of Minimal Residual Disease Negative Complete Remission (MRD-CR) and Allogeneic Stem Cell Transplant on Safety and Clinical Outcome of CD19-Targeted 19-28z CAR Modified T Cells in Adult Patients with Relapsed, Refractory B-Cell ALL." Dr. Park will provide updated results on a total of 46 patients treated with JCAR015 in B-cell ALL. Key takeaways include:

Overall complete response (CR) was reported in 37/45 (82%) evaluable patients and minimal residual disease (MRD)-negative CR was reported in 30/36 (83%) patients who achieved a CR and were evaluable for MRD analysis.

r/r B-cell ALL patients who achieve MRD-negative CR have improved survival compared to those who achieve MRD-positive CR.
r/r B-cell ALL patients who achieve MRD-negative CR appear to have comparable survival whether or not they proceed to an allogeneic stem cell transplant.

JCAR015 has consistent efficacy across multiple high risk subgroups, including elderly and multiple relapsed patients.
Severe cytokine release syndrome (CRS) was observed in 11/46 (24%) patients. Severity of CRS correlated with disease burden and was generally reversible.

Grade 3/4 neurotoxicity was observed in 13/46 (28%) patients. As previously disclosed, Grade 5 toxicity was observed in 3/46 (6%) patients, and was assessed to be unrelated to JCAR015 treatment in one of these patients.

In a poster presentation on Monday, December 7, 2015, Cameron J. Turtle, MBBS, Ph.D. of the Fred Hutchinson Cancer Research Center will present, "Addition of Fludarabine to Cyclophosphamide Lymphodepletion Improves In Vivo Expansion of CD19 Chimeric Antigen Receptor-Modified T Cells and Clinical Outcome in Adults with B-Cell Acute Lymphoblastic Leukemia." Dr. Turtle will provide updated results on a total of 30 patients treated with JCAR014 against r/r B-cell ALL. Key takeaways include:

The addition of fludarabine to cyclophosphamide-based lymphodepletion to a defined cell product improves CAR T cell expansion, persistence, response rate, and disease-free survival in r/r B-cell adult ALL.

The CR rate as documented by flow cytometry was 27/29 (93%) of evaluable patients with r/r B-cell ALL. After the addition of fludarabine, 17/17 (100%) of patients had a CR and a complete molecular remission (CMR) rate, as measured by flow cytometry.
Severe CRS was reported in 7/30 (23%) and Grade ≥3 neurotoxicity was noted in 15/30 (50%) ALL patients.
The risk-stratified dosing of JCAR014 is potent, feasible, and reduced the incidence of severe CRS.

ASH Investor and Analyst Event and Webcast
The Juno ASH (Free ASH Whitepaper) Investor and Analyst Event and webcast will be held Monday, December 7, 2015 at 8:30 p.m. Eastern Time. The webcast can be accessed live on the Investor Relations page of Juno’s website, www.JunoTherapeutics.com, and will be available for replay for 30 days following the event.

About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s chimeric antigen receptor (CAR) and T cell receptor technologies (TCR) genetically engineer T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. Juno’s TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell. JCAR014 and JCAR015 are investigational product candidates and their safety and efficacy have not been established.

CytRx Nominates Next Clinical Drug Candidate DK049

On December 7, 2015 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that it has selected its next drug, designated DK049, for clinical development in 2016 (Press release, CytRx, DEC 7, 2015, View Source [SID:1234508465]).

DK049 was created using CytRx’s novel LADR (Linker-Activated Drug Release) technology that allows the drug to bind to albumin in the body’s bloodstream and controls its release at the site of the tumor. The LADR technology used with DK049 employs a two-stage linker that utilizes both pH sensitivity and acts enzymatically to allow release of its cytotoxic drug payload which extends the duration of exposure in tumors. Prolonged inhibition of tumor growth has been demonstrated in human tumor xenograft models of pancreatic cancer, non-small cell lung cancer and ovarian cancer at doses that lack apparent toxicity. As an example of the LADR technology’s capability, human ovarian tumor xenograft models received 85% less drug than a known chemotherapy comparator, yet at the end of the study, DK049-treated tumors were an average 13 times smaller than the chemotherapy-treated animals. These data have been submitted for presentation at the American Association of Cancer Research Annual Meeting in April 2016. Additionally, CytRx has applied for patents for both its LADR technology and DK049 itself.

"We believe that our LADR technology is the next advancement in linker-controlled drug release to be used with both antibody-drug conjugates and albumin-binding approaches, " commented Dr. Felix Kratz, Vice President of Drug Discovery at CytRx. "The ability to adjust the structure and composition of our linkers allows CytRx to attach a variety of lethal agents that include modified standard chemotherapies as well as highly potent agents currently used in antibody-drug conjugates."

"In only its first year, our Drug Discovery Group has created a technology that is capable of providing CytRx with a clinical pipeline for years to come," said Steven A. Kriegsman, Chairman and CEO of CytRx Corporation. "Their creation of DK049 was accomplished very rapidly due to the intelligent drug design and experience of Dr. Kratz’s group. We are confident that their progress with the LADR technology will be a key value driver for CytRx in the future."

CytRx’s LADR technology has several advantages over current linkers:

It allows prolonged drug exposure with accumulation at the site of the tumor.
The linker reduces drug release in healthy cells.
The controlled release allows delivery of payloads that are 10-1000 times more potent than standard chemotherapies.
The LADR conjugates can evade traditional drug resistance mechanisms.

Merck Decides Not to Pursue Evofosfamide Further in Soft Tissue Sarcoma and Pancreatic Cancer

On December 7, 2015 Merck, a leading science and technology company, reported that it is not planning to file for approval of evofosfamide in advanced soft tissue sarcoma and advanced pancreatic adenocarcinoma (Press release, Merck KGaA, DEC 7, 2015, View Source [SID:1234508464]).

The decision was made in light of the results from two Phase III studies of evofosfamide in combination with chemotherapy in these two types of cancer, as reported by Threshold Pharmaceuticals Inc. today. Merck will now be redeploying its resources into high-profile future products, such as avelumab* and all other priority programs in oncology, immuno-oncology and immunology.

"Despite seeing signs of activity in pancreatic cancer, pre-specified primary endpoints were not met in both studies and therefore the data do not support filing in these indications," said Luciano Rossetti, Head of Global Research and Development of Merck’s biopharma business. "We decided today not to pursue investigation of evofosfamide in soft tissue sarcoma and pancreatic cancer, and we will be making a quick decision on the future of the ongoing evofosfamide clinical program."
Details of the two Phase III studies will be shared with the scientific community once the data have been further analyzed.

"Today’s results are disappointing for patients. Yet we are confident in our pipeline and will reallocate evofosfamide resources to accelerate other key programs in oncology and immuno-oncology," said Rossetti.

Merck’s pharmaceutical pipeline is focusing on oncology, immuno-oncology and immunology. In immuno-oncology, Merck, together with Pfizer, is researching avelumab, an investigational anti-PD-L1 antibody, in more than 15 tumor types.

*Avelumab is the proposed International Nonproprietary Name for the anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe tumor hypoxic conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic.

Merck signed a global license and co-development agreement for evofosfamide with Threshold Pharmaceuticals, Inc. in February 2012, with an option for Threshold to co-commercialize in the U.S.