Tmunity Announces Exclusive License and Research Collaboration with Children’s Hospital of Philadelphia to Advance GPC2 CAR-T Cell Therapy for Neuroblastoma

On October 1, 2019 Tmunity Therapeutics, Inc., a private clinical-stage biotherapeutics company focused on saving and improving lives by delivering the full potential of next-generation T-cell immunotherapy, reported it has entered into an exclusive license and research collaboration agreement with Children’s Hospital of Philadelphia (CHOP) to advance a glypican 2 (GPC2) chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of neuroblastoma, a rare cancer that affects the developing nervous system (Press release, Tmunity Therapeutics, OCT 1, 2019, View Source [SID1234539992]). The therapy also has expansion potential in medulloblastoma and small cell lung cancer, among several other pediatric and adult cancers that express an abundance of the GPC2 protein on their cell surface.

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John Maris, MD and Kristopher Bosse, MD, pediatric oncologists and physician-scientists at CHOP, identified and validated the oncoprotein GPC2. It is highly expressed on neuroblastomas but not detectable at appreciable levels in normal childhood tissues. In a seminal paper published in Cancer Cell in 2017, the CHOP team determined that GPC2 may be less susceptible to immune escape mechanisms due to its requirement for neuroblastoma proliferation. Their work validated GPC2 as a nonmutated neuroblastoma oncoprotein and established a strong foundation for GPC2 as an immunotherapeutic target. "This new collaboration builds upon our prior studies and pairs Tmunity’s experience in engineering and developing CAR-T cells with CHOP’s expertise in the biology of this family of cell surface molecules across neuroblastoma and several other cancers," said Dr. Bosse, an Assistant Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and CHOP.

"The collaboration with CHOP expands our network of world-class academic collaborators and progresses our strategy to build a pediatric oncology franchise and advance novel T-cell therapies for devastating diseases. By combining the scientific insights and research at CHOP with the T-cell development, regulatory, and manufacturing capabilities and expertise at Tmunity, we created a formidable team to attack this deadly cancer," said Usman "Oz" Azam, MD, President and Chief Executive Officer of Tmunity. "We look forward to working with Dr. Maris, Dr. Bosse, and their teams to advance GPC2 T-cell therapy and offer hope to patients with limited options."

Neuroblastoma is a rare cancer that affects the development of the nervous system by attacking immature nerve cells as early as the embryonic stage. Each year, about 800 children are diagnosed with neuroblastoma in the U.S., and overall survival rates are less than 50%. Current chemotherapy options for these patients are limited and highly toxic, which highlight the urgent need for new treatments for this disease, which improve overall survival and reduce long-term toxicity.

"We are excited to collaborate with Tmunity to accelerate the development of GPC2 for neuroblastoma," said John Maris, MD, co-head of the Pediatric Cancer Dream Team and Giulio D’Angio Chair in Neuroblastoma Research at CHOP. "Our studies have confirmed that GPC2 is an important target in neuroblastoma and other aggressive malignancies. We look forward to one day bringing, GPC2 T-cell therapies to the clinic and to patients in need."

Under the terms of the agreement, Tmunity will collaborate with CHOP to initiate IND-enabling studies and advance quickly into the clinic. Tmunity will be responsible for leading the development, manufacturing, regulatory, and commercialization of the GPC2 T-cell therapy. The majority of the preclinical studies will be performed by CHOP. Deal terms were not disclosed.

Rocket Pharmaceuticals Announces Participation at the Chardan 3rd Annual Genetic Medicines Conference

On October 1, 2019 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) ("Rocket"), a leading U.S.-based multi-platform clinical-stage gene therapy company, reported that Gaurav Shah, M.D., Chief Executive Officer and President of Rocket is scheduled to present on Tuesday, October 8, 2019, at 11:00 a.m. Eastern Time at the Chardan 3rd Annual Genetic Medicines Conference, New York, N.Y (Press release, Rocket Pharmaceuticals, OCT 1, 2019, View Source [SID1234539991]).

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Numab and Eisai Enter Into a Global Research and Option Agreement to Discover and Develop Multi-Specific Antibody Immunotherapies for Cancer

On October 1, 2019 Numab Therapeutics AG (Numab) reported the initiation of a partnership with Eisai, Co., Ltd (Eisai), under a research and option agreement, to discover and develop novel multi-specific antibody immunotherapies for cancer, using Numab’s proprietary MATCH platform (Press release, Numab, OCT 1, 2019, View Source [SID1234539990]).

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Under the terms of the agreement, Eisai has the option to acquire an exclusive license to develop and commercialize novel multi-specific antibody-based molecules that emerge from their research collaboration with Numab. In exchange, Numab will receive from Eisai an upfront payment and research funding and is eligible to receive success fees, milestone payments and tiered royalties on sales.

Dr. David Urech, CEO of Numab, said: "We are excited to enter into this partnership with Eisai, a company with a distinguished track-record of providing innovative treatment options for patients suffering from cancer. We look forward to collaborating with Eisai and applying Numab’s MATCH platform with the goal of leveraging multi-specific technology to generate cancer therapeutics that provide superior efficacy and safety compared to benchmark immunotherapies."

Dr. Takashi Owa, Vice President, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai, said: "We highly value this partnership with Numab, whose versatile technology platform can produce plug-and-play multi-specific immunotherapies with outstanding biophysical properties and efficacy-to-safety profiles. Like Numab, we believe that engineering multi-specific drugs is a very promising strategy to enhance patient responses and overcome several limitations faced by mono-specific drugs and combinations thereof. We are excited to be working together with Numab to potentially bring next-generation antibody drugs to patients."

Servier acquires non-Hodgkin B-cell lymphoma treatment PIXUVRI® (pixantrone) from CTI BioPharma, strengthening the Servier oncology portfolio

On October 1, 2019 Servier, an independent international pharmaceutical company, reported the acquisition of PIXUVRI from CTI BioPharma (Press release, Servier, OCT 1, 2019, View Source [SID1234539989]). PIXUVRI is a treatment for adult patients with multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphoma. Servier and CTI Biopharma completed an Asset Purchase Agreement which transferred worldwide rights of PIXUVRI to Servier. Servier commercialized PIXUVRI globally, in all countries where the drug was approved under an exclusive license from CTI BioPharma.

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"The acquisition of PIXUVRI is an important step towards Servier’s long-term strategy to become a key player in oncology. Within oncology, one of our key focuses is hematology, and we now have two medicines that are marketed globally alongside a strong and innovative pipeline of drug candidates which includes CAR-T therapies," said Claude Bertrand, Executive VP, Global Head of R&D at Servier. "As part of our strategy, we are committed to invest 50% of our R&D budget in oncology."

Non-Hodgkin lymphoma (NHL) is a blood cancer that affects the lymphatic system, it can occur in different parts of the body from the lymph nodes in the neck to the liver or spleen, but also in other organs such as the stomach, small bowel, bones, brain, testicles or skin.1 Globally there are over 500,000 new cases of NHL a year; it is both the 11th most commonly diagnosed cancer and cause of cancer death.2

"We have a strong commitment to providing effective solutions for patients living with cancer. PIXUVRI is an effective treatment that received standard European marketing authorization in June, and today marks a new step towards achieving Servier’s long term goals. We will ensure that patients will continue to have access to PIXUVRI", said Eric Falcand, VP, Global Head of Business Development & Licensing at Servier. "We are continuing to strengthen our oncology portfolio through our R&D efforts and strategic alliances."

#ENDS#

About PIXUVRI (pixantrone)

PIXUVRI is a cytotoxic medicine that works by interfering with the DNA within cells and preventing them from making more copies of DNA. This means that the cancer cells cannot divide and eventually die.3 PIXUVRI is indicated in the European Union as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphoma.3 PIXUVRI is also approved in Iceland, Israel, Liechtenstein, Myanmar, Norway, Pakistan, Russia and Ukraine.

PIXUVRI is mentioned in the ESMO (Free ESMO Whitepaper) guidelines as an anthracycline-like drug with reduced cardiotoxicity, which demonstrated some efficacy in heavily treated patients.4

More detail is available in the summary of the European public assessment report (EPAR) on the EMA website at www.ema.europa.eu.

Trovagene Presents Overview of Phase 1b/2 Trial of Onvansertib in Patients with KRAS-Mutated Metastatic Colorectal Cancer (mCRC) at ESMO

On October 1, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis) for the treatment of various cancers including prostate, colorectal and leukemia, reported the presentation of its Phase 1b/2 trial evaluating onvansertib in combination with FOLFIRI and Avastin (bevacizumab) in patients with KRAS-mutated metastatic Colorectal Cancer (mCRC) (Press release, Trovagene, OCT 1, 2019, View Source [SID1234539987]).

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The trial overview, featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress showed the supportive preclinical data underlying the scientific rationale for the trial, as well as the trial design and primary safety and efficacy endpoints. In addition, early biomarker data demonstrates proof-of-concept that patient response can be monitored by a non-invasive blood test to quantitate the KRAS mutation burden within one week following initial dosing with onvansertib.

"Although early in the trial, the potential to bring a much-needed new treatment option to patients with KRAS-mutated mCRC with the combination of these drugs is promising," said Heinz-Josef Lenz, MD, FACP, Professor of Medicine, J. Terrence Lanni Chair in Gastrointestinal Cancer Research, Co-Director, USC Center for Molecular Pathway and Drug Discovery. "As of September 1, 2019, four patients have been treated and one has successfully completed their first cycle of treatment. We believe onvansertib may provide clinical benefit for patients who are faced with a poor prognosis and for whom therapeutic options are limited."

Colorectal cancer (CRC) is the second leading cause of cancer mortality in the U.S. Despite significant progress in the treatment of mCRC, the majority of patients with metastatic disease succumb to the disease. Therefore, improving the effectiveness of treatments is critical in changing the outcomes for this patient population. Approximately 50% of mCRC has the KRAS mutation. The efficacy of second-line therapy in terms of survival prolongation and response remains very limited, especially in this population, where there is only a 5% response rate.

Presentation Highlights

Metastatic Colorectal Cancer:

Tumor biomarkers drive therapy decisions for 1st and 2nd line mCRC therapy
~50% of mCRC is KRAS-mutated
Standard second-line therapy in KRAS mutated patients is chemotherapy (FOLFOX/FOLFIRI) + Bevacizumab
Second-line therapies have only a ~5% response rate in mCRC
Primary Endpoints:

Phase 1b: Assess the safety and preliminary efficacy of onvansertib in combination with FOLFIRI and bevacizumab and identify the recommended Phase 2 dose (RP2D)
Phase 2: Evaluate the efficacy of onvansertib in combination with FOLFIRI and bevacizumab based on objective response rate (ORR) in patients who receive at least 1 cycle (2 courses) of treatment
About the Phase 1b/2 Clinical Trial of Onvansertib in mCRC
The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, will evaluate the safety and efficacy of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab). Up to 44 patients, with a confirmed KRAS mutation, metastatic and unresectable disease, who have failed/intolerant of treatment with FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab), will be enrolled. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.

About Onvansertib
Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.

Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.

Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.