On Sept 14, 2020 SpringWorks Therapeutics a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the company has entered into a clinical collaboration and supply agreement with Janssen Biotech, Inc. (Janssen) to evaluate SpringWorks Therapeutics’ investigational gamma secretase inhibitor (GSI), nirogacestat, in combination with Janssen’s bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, teclistamab, in patients with relapsed or refractory multiple myeloma. (Press release, Janssen Research & Development, SEP 14, 2020, View Source [SID1234574085]).

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Gamma secretase inhibition prevents the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase the cell surface density of BCMA and reduce levels of soluble BCMA, which may enhance the activity of BCMA-targeted therapies, including CD3 bispecific antibodies.

"We are delighted to enter into this collaboration with Janssen to study nirogacestat in combination with teclistamab," said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. "We now have three collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, an allogeneic CAR-T cell therapy and now a bispecific antibody. This collaboration is an important step in continuing to advance our goal of developing nirogacestat as a best-in-class BCMA potentiator."

Under the terms of the agreement, Janssen will sponsor and conduct the Phase 1 study to evaluate the safety, tolerability and preliminary efficacy of the combination, and will assume all costs associated with the study, other than expenses related to the manufacturing of nirogacestat. SpringWorks Therapeutics will also form a joint oversight committee with Janssen. Pending discussions with regulators, the study is anticipated to commence by early 2021.

In addition to its ongoing clinical collaborations with BCMA-directed therapies, SpringWorks is also currently conducting a global Phase 3, double-blind, randomized, placebo-controlled clinical trial (the DeFi Trial) to evaluate nirogacestat in adults with progressing desmoid tumors.

On September 14, 2020 Ziopharm Oncology, Inc. ("Ziopharm" or "the Company") (Nasdaq:ZIOP) reported that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation to Ad-RTS-hIL-12 with veledimex (Controlled IL-12) for the investigational treatment of diffuse intrinsic pontine glioma (DIPG), a lethal brain tumor occurring in the pontine region of the brain (Press release, Ziopharm, SEP 14, 2020, View Source [SID1234569925]). DIPG accounts for approximately 10 to 15 percent of all cases of brain tumors in children. The Rare Pediatric Disease Designation program is intended to encourage the development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.

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"We are delighted to have received the Rare Pediatric Disease Designation for Controlled IL-12 from the FDA. This milestone for Ziopharm emphasizes the significant unmet need for children living with DIPG," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of Ziopharm. "Currently, there are no viable treatment options for this type of brain tumor. We are working with the FDA to advance Controlled IL-12 as a new gene therapy for this aggressive disease, which has historically been largely seen as incurable."

The FDA grants Rare Pediatric Disease Designation for serious and life-threatening diseases that primarily affect children ages 18 years or younger and fewer than 200,000 people in the United States. If Ziopharm’s Biologics License Application (BLA) for Controlled IL-12 in DIPG is approved, the Company may be eligible to receive a priority review voucher from the FDA, which can be redeemed to obtain priority review for any subsequent marketing application or may be sold or transferred to another company for their program.

About DIPG
In children, the incidence of brain cancer is approximately 4.84 per 100,000, according to the National Cancer Institute. Glioma in the pontine region of the brain, or DIPG, accounts for approximately 10-15 percent of all cases of pediatric brain tumors, with about 150-300 new diagnoses per year in the United States.1 Median survival ranges from 8-11 months.2 There are no curative options.

About Controlled IL-12 (Ad-RTS-hIL-12 plus veledimex)
Ziopharm’s Controlled IL-12 platform is an investigational gene therapy designed to induce and control the production of human interleukin 12 (hIL-12), a master-regulator of the immune system. The Company has treated more than 175 patients, including more than 125 patients with rGBM, with Ad-RTS-hIL-12 plus veledimex and administered more than 1,300 doses of veledimex across three types of solid tumors, building a significant safety profile, mechanistic dataset and evidence of anti-tumor effects.

Controlled IL-12 is being studied in a phase 1/2 trial (NCT03330197) designed to evaluate the safety and tolerability of a single intratumoral injection of Ad-RTS-hIL-12 given with up to 14 days of oral veledimex in children with gliomas. Up to 12 patients with DIPG may be enrolled in phase 1 of the study, which is being conducted at leading pediatric cancer centers across the United States, including Lurie Children’s Hospital in Chicago, Dana-Farber Cancer Institute in Boston and University of California in San Francisco.

On September 14, 2020 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported the hosting of a Key Opinion Leader (KOL) Event to discuss the medical need in pancreatic cancer and the potential role of eryaspase in this setting (Press release, ERYtech Pharma, SEP 14, 2020, View Source [SID1234568713]).

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On September 14, 2020 Silence Therapeutics plc, AIM:SLN and Nasdaq: SLN ("Silence" or "the Company"), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported the appointment of Mark Rothera as President and Chief Executive Officer (CEO) and Board member, effective immediately (Press release, Silence Therapeutics, SEP 14, 2020, View Source [SID1234568597]). Iain Ross, who has been Executive Chairman since December 2019, has today assumed his previous position of Non-Executive Chairman.

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Mr. Rothera brings more than 30 years of experience in the biopharmaceutical industry, with a strong record of commercial and operational leadership, including driving the successful build of multiple biotech companies, predominantly in the field of rare or specialty diseases. Prior to joining Silence, Mr. Rothera served as CEO of Orchard Therapeutics (Orchard), where he oversaw its transformation from a small U.K.-based, privately held company with two clinical-stage programmes into a leading gene therapy company with seven clinical-stage programmes and fully integrated capabilities. Under his leadership, Orchard completed an initial public offering of American Depositary Shares on the Nasdaq Global Market and during his tenure that company secured more than $600 million in financing and grew from a market capitalization of $250 million to more than $1.7 billion at its peak.

Prior to Orchard, Mr. Rothera served as Chief Commercial Officer of PTC Therapeutics (PTC), where he helped transition that company from a privately held R&D biotechnology company to a publicly traded, commercial-stage company with a global footprint, including the successful launch of two rare disease therapies. He also previously served as Global President of Aegerion Pharmaceuticals Inc. and Vice President and General Manager of commercial operations at Shire Human Genetic Therapies for Europe, Middle East and Africa. Mr. Rothera received an M.A. in Natural Sciences from Cambridge University and an M.B.A. from the European Institute for Business Administration (INSEAD).

Based out of Silence’s New York City office, Mr. Rothera will lead the continued global expansion of the Company. His appointment follows the completion of Silence’s Nasdaq listing on 8 September 2020 and aligns with the strategy of increasing the Company’s presence in the United States.

Iain Ross, Chairman of Silence Therapeutics plc, said: "On behalf of the Silence Board and the entire Silence team, I welcome Mark to the Company. Following a thorough search, Mark’s appointment reflects his proven leadership skills and strong track record in growing successful biotechnology companies and building shareholder value. I believe he will now provide the leadership necessary to grow Silence into a leading international biotechnology company built upon our innovative siRNA technology platform, proprietary product pipeline and validating industry partnerships.

"On a personal note, and on behalf of the Board, I would like to thank the management team and staff at Silence for their support, hard work and tremendous resilience during the current COVID-19 pandemic and over the past nine months whilst I have been Executive Chairman. The Company has made great strides during this period, and is now in a strong position, both operationally and financially, and ready for Mark to take the helm."

Mark Rothera, President and CEO of Silence Therapeutics plc, added: "It is an honour to take the role of leading Silence at this time in the Company’s history. I believe the Company is poised to capitalise on its important siRNA technology platform, pipeline and research capabilities built over 18 years, and position itself as a leader in the RNAi field. The Company has made great strides under Iain’s leadership and I look forward to working with the Board, the management team and Silence employees to build upon this momentum."

On September 14, 2020 A team of scientists led by aresearcher at the Case Western Reserve University School of Medicine reported that it is making strides to fight deadly metastatic breast cancer by combining nanotechnology with immunotherapy (Press release, Case Western Reserve University, SEP 14, 2020, View Source [SID1234565160]).

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Efstathios "Stathis" Karathanasis, an associate professor of biomedical engineering, is directing the novel technique—sending nanoparticles into the body to wake up "cold" tumors so they can be located and neutralized by immune cells. The team also includes researchers from Cleveland Clinic and Duke University.

Nanotechnology manipulates matter at the nanoscale—microscopically at dimensions measured by nanometers or one-billionth of a meter—to create structures, devices and systems for medical and other uses.

Immunotherapy uses drugs to help a patient’s immune system fight cancer, as opposed to chemotherapy, which uses drugs to directly kill cancer cells, according to the National Cancer Institute (NCI).

The NCI recently awarded a five-year, $3 million grant to Karathanasis and his team to continue their research, initially on animal models with an eye toward human trials. Much of the groundwork behind the project is described in a paper published in Cancer Research, the official journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

"We believe our work shows that this combination of nanotechnology with cancer immunotherapy encompasses an inherent promise to treat the most hard-treat metastatic cancers," Karathanasis said. "Our work has been to design a nanoparticle that triggers an activation of antigen-presenting cells in the tumor. Within a few weeks, the patient can have adapted T cells that recognize and fight the cancer."

Metastatic cancer problem
Breast cancer is the second-leading cause of death from cancer in women in the United States (behind skin cancer), killing more than 42,000 a year; metastatic breast cancer will cause the vast majority of those deaths. Also called Stage IV Cancer, it is breast cancer that has spread to another part of the body, most commonly the liver, brain, bones, or lungs.

Metastatic cancer cells are often considered stealth killers, "ticking time bombs that remain dormant until they emerge as incurable tumors," Karathanasis said.

That means one of the most difficult aspects of diagnosing and treating metastatic breast cancer is that the cells often cannot be found until it is too late for successful treatment.

"They are just sitting there, without dividing, or doing it so slowly that they cannot be detected or treated by any current therapy," Karathanasis said.

And immunotherapy, while offering cancer patients new hope as the science continues to develop, is only successful about 20% of the time.

"When immunotherapy works, it’s highly effective by using our most potent weapon, our own immune system. But cancer cells hijack and recruit the local immune cells in tumors making them dysfunctional, unfortunately," Karathanasis said. "If there are no danger signals from the body, the immune system doesn’t know there is an enemy."

Nanotechnology solution
Karathanasis, an engineer by training who began to work on nanotechnology solutions to medical problems about two decades ago, has devised a way to get the tumor to notify the body’s innate immune system—and the other immunotherapeutic interventions—of its presence.

Initially, when a tumor appears in the body, our immune cells should recognize it and send out cells to try to "kill the enemy" and also "memorize" it, so they can come back and kill it again in the case of tumor recurrence, Karathanasis said.

But then, the tumor adapts and essentially goes undercover, repressing any immune cells, so that it cannot be found by the standard surveillance of the immune system.

Karathanasis and his team have engineered a nanoparticle to "trigger the antigen-presenting cells in the tumor to start generating fresh signals," he said.

The research team also includes: William Schieman, the Goodman-Blum Professor in Cancer Research, Case Western Reserve School of Medicine; Li Lily Wang, associate staff, Cleveland Clinic Lerner Research Institute; and Christopher Hoimes (Duke University School of Medicine).

"We are taking a cold tumor and making it ‘hot’ again," Karathanasis said. "We are unlocking the immune system, which has been repressed by the tumor. We regenerate the cycle of immunity."