On November 15, 2018 Boehringer Ingelheim and Epizyme, Inc. (Nasdaq: EPZM) reported a new global collaboration focused on the research, development and commercialization of novel small molecule inhibitors directed toward two previously unaddressed epigenetic targets as potential therapies for people with cancer (Press release, Boehringer Ingelheim, NOV 15, 2018, View Source [SID1234531361]). Specifically, these targets are enzymes within the helicase and histone acetyltransferase (HAT) families that when dysregulated have been linked to the development of cancers that currently lack therapeutic options.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Boehringer Ingelheim’s collaboration with Epizyme furthers our strategic vision to profoundly impact the oncology treatment landscape by enabling a new generation of precision medicines," said Clive R. Wood, Ph.D., Senior Corporate Vice President, Discovery Research, Boehringer Ingelheim. "We are excited to launch this partnership with Epizyme and to work together with them to advance epigenetic inhibitors that have the potential to transform the lives of patients and help win the fight against difficult-to-treat cancers."

Epigenetic modification affects how genes are biologically regulated. More than half of cancers can stem from functional errors in epigenetic modification. In particular cases, epigenetic dysregulation is associated with alterations in specific components of gene regulation, which can be used to identify patients most likely to benefit from the therapy. What makes both targets compelling is not only the clear role they play in cancer but that both targets have patient stratification biomarkers, which will enable a focus on the patients most likely to benefit from these potential treatments. Epizyme is a leader in the discovery of the roles of such enzymes and their development as therapy targets.

"This partnership with Boehringer Ingelheim to develop treatments for two novel epigenetic targets, which have been historically viewed as undruggable, further validates the promise of epigenetics for oncology and our pioneering leadership in this field," said Robert Bazemore, president and chief executive officer of Epizyme. "By combining our innovative target identification and research capabilities with Boehringer Ingelheim’s world-class drug development and commercialization expertise, we are aiming to realize the full potential of these targets and our platform, while continuing to focus on executing development of our lead program in multiple ongoing and planned clinical trials."

The collaboration has a strategic goal to focus on lung and other solid tumor cancers in patients with defined mutations, sub-populations that currently lack precision medicine treatments. Under the terms of the agreement, Boehringer Ingelheim and Epizyme will jointly research and develop a helicase program, with both parties sharing U.S. commercialization responsibilities and Boehringer Ingelheim assuming responsibility for commercialization outside the U.S. Epizyme and Boehringer Ingelheim will share research responsibilities for the HAT program, with Boehringer Ingelheim assuming responsibility for worldwide development and commercialization.

Epizyme will receive an upfront payment of $15 million and an additional $5 million in research funding in 2019. Epizyme is eligible to receive more than $280 million in additional payments for research, development, regulatory and commercial milestones. For the helicase program, Epizyme will fund a portion of the global development costs, retain a share of U.S. profits and receive tiered royalties on ex-U.S. sales. For the HAT program, Epizyme is eligible to receive tiered royalties on worldwide sales.

On November 15, 2018 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported the presentation of clinical and preclinical data supporting the development of TP-0903 for the treatment of patients with solid tumors (Press release, Tolero Pharmaceuticals, NOV 15, 2018, View Source [SID1234531405]). TP-0903 is an oral, small molecule inhibitor of the AXL receptor tyrosine kinase. Key findings from syngeneic mouse models suggest that TP-0903 has immune activating potential leading to enhanced host immune responses in tumor models.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The data will be presented at the 2018 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium in Dublin. Posters will be on display from 10:00 a.m. to 2:00 p.m. GMT on Nov. 16 in the Exhibition Hall of the Convention Centre Dublin.

"There is a significant need to develop new cancer therapeutic solutions aimed at strengthening the body’s own immune response," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "AXL kinase is an important oncolytic target; we are encouraged by the findings of TP-0903 showing the inhibition of AXL kinase, demonstrating enhanced host immunity. We look forward to further developments of TP-0903 in counteracting AXL-mediated effects."

The data show that TP-0903 treatment alters tumors by suppressing the mesenchymal phenotype of the cancer cells and favoring a tumor microenvironment amenable to an immune response. Preclinical models in immune competent animals show modulation of immune cell populations, including neutrophils, regulatory T-cells, and dendritic cells, in the tumors. Additionally, the predictive power of soluble AXL levels in the serum of cancer patients as a biomarker to select patients likely to benefit from TP-0903 treatment will be presented.

Recent data suggest that AXL kinase is involved in tumor cell proliferation and development of resistance to chemotherapeutics. TP-0903 is an AXL receptor tyrosine kinase inhibitor, which has showed nanomolar activity in biochemical assays. In this preclinical study, the immune modulating capabilities were assessed using immunohistochemical and real-time PCR techniques in syngeneic mouse models of solid tumors.

The associated abstract #413, PB-076, is available on the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) meeting program website.

About TP-0903
TP-0903 is an investigational oral, small molecule inhibitor of the AXL receptor tyrosine kinase (RTK), which has demonstrated effectiveness in cell-based and animal models of human cancers. The first-in-human Phase 1/1b study is underway identifying the safety and tolerability profile of TP-0903. In addition, the study is analyzing the pharmacodynamics of TP-0903 by assessing biomarkers in patients’ samples before and after treatment with TP-0903, including markers of immune suppression.

About AXL Kinase
AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers. It plays a key role in tumor cell proliferation, survival, metastasis, cellular adhesion and avoidance of the immune response. The overexpression of AXL is associated with a poor patient prognosis and drug resistance.1,2

On November 15, 2018 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205), a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported its unaudited revenues for the third quarter of 2018 (Press release, Nanobiotix, NOV, 15, View Source [SID1234531455]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Activity and results
Total revenue for the third quarter of 2018 amounted to € 21,816. This brings total revenue for the first nine months of 2018 to € 95,120, which is in line with the Company’s expectations.
All of the revenues generated by the Company during the third quarter of 2018 come from services that Nanobiotix
crossed-charged to its partners in accordance with our agreed upon development program operational activities.
In July 2018, Nanobiotix launched a non-dilutive financial partnership with the European Investment Bank (EIB) to boost its research, development and innovation activities. The financing agreement permits the Company to borrow up to €40 million in loans from EIB over the next five years subject to the Company’s achievement of a set of agreed performance criteria. We expect this financing agreement to enable Nanobiotix to accelerate both the development of the Company’s NBTXR3 clinical trial in advanced Head and Neck cancers and to support its European go-to-market strategy.

In September 2018, Nanobiotix presented an update on data from its NBTXR3 development program at the International Conference on Immunotherapy Radiotherapy Combinations. The presentation included updated data related to the Company’s follow-up for its Phase I/II clinical trial in advanced Head and Neck cancers in elderly and frail patients ineligible for cisplatin or intolerant to cetuximab. The data suggests the potential of NBTXR3 to impact survival for this advanced cancer patient population. In addition, the Company presented data obtained from the immuno biomarker study in its randomized Phase II/III clinical trial in soft tissue sarcoma. This data indicated that NBTXR3 activated by EUI- 1202982973v22 radiation therapy could modulate the antitumor immune response.
Finally, the Company’s in vivo investigation of NBTXR3’s mode of action inducing distant immune response on CT26
tumoral model produced data that continues to support the rationale for the use of NBTXR3 activated by radiation
therapy to seek to transform tumors into an in situ cancer vaccine and its potential use in combination with
immunotherapeutic agents.
***
Next financial press release: revenue for Q4 2018 by February 28, 2019
About NBTXR3
NBTXR3 is a first-in-class product designed to destroy, when activated by radiotherapy:
• tumors through physical cell death
• metastasis due to immunogenic cell death leading to activation of the immune system
NBTXR3 has a high degree of biocompatibility, requires one single administration before the whole radiotherapy treatment and
Nanobiotix believes it has the ability to fit into current worldwide standards of radiation care.
Nanobiotix’s broad clinical program includes 10 patient populations evaluated in 7 clinical trials.
In June 2018, Nanobiotix established human proof of concept for this first-in-class product in its Soft Tissue Sarcoma (STS) Phase III
clinical trial.
NBTXR3 is actively being evaluated in head and neck cancer with locally advanced squamous cell carcinoma of the oral cavity or
oropharynx in elderly and frail patients that are unable to receive chemotherapy or cetuximab and have very limited therapeutic
options. Promising results have been observed from the ongoing Phase I/II trial regarding the local control of tumors.
Nanobiotix is running an Immuno-Oncology development program. In the United States, Nanobiotix has received approval from the
U.S. Food and Drug Administration (FDA) to launch a clinical study of NBTXR3 activated by radiotherapy in combination with anti-PD1
antibodies in lung, and head and neck cancer patients (head and neck squamous cell carcinoma and non-small cell lung cancer).
The other ongoing NBTXR3 trials are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally
advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent
chemotherapy, and prostate adenocarcinoma.
The first market authorization process (CE Marking) is ongoing in Europe in the STS indication.

On November 15, 2018 Epizyme, Inc. (Nasdaq: EPZM), a clinical-stage company developing novel epigenetic therapies, reported that management will host a conference call to discuss corporate updates today at 8:30 a.m. ET (Press release, Epizyme, NOV 15, 2018, View Source [SID1234531362]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 5172457. A live webcast will be available in the investor section of the company’s website at www.epizyme.com. The webcast also will be archived for 60 days following the call and presentation

On November 15, 2018 Rakuten Aspyrian, a biotechnology company developing precision-targeted cancer therapies based on its proprietary Photoimmunotherapy platform, reported the appointment of Mickey Mikitani as chief executive officer (Press release, Rakuten Aspyrian, NOV 15, 2018, View Source [SID1234531388]). Mr. Mikitani, a global business leader, will also continue in his role of chairman. In conjunction, former CEO Miguel Garcia-Guzman, Ph.D. will transition to serve as Rakuten Aspyrian’s vice chairman and chief scientific officer to continue to build the company’s pipeline and drive innovation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Rakuten Aspyrian also announced the appointment of Takashi Toraishi, Ph.D. as chief operating officer. Dr. Toraishi will oversee clinical trials and commercialization of Rakuten Aspyrian’s products, as well as manage the growth of the organization.

"With our Photoimmunotherapy platform, Rakuten Aspyrian holds tremendous potential to offer alternative options for treating cancer," said Mr. Mikitani. "As CEO, I will harness this potential as we build a fully integrated biopharmaceutical company with research, development and world-wide commercialization capabilities. Our mission is to develop and commercialize a strong pipeline of treatment options based on Photoimmunotherapy to create a new platform for cancer treatments."

Mr. Mikitani joined the company as chairman in 2016 and has provided strategic direction and investment to support its corporate and clinical development. He is also the Chairman and CEO of Rakuten, Inc. [RKUNF], a leading Japanese global innovation company in e-commerce, communications and fintech, with the mission to contribute to society by creating value through innovation and entrepreneurship. Rakuten is also recognized as the Official Innovation and Entertainment Partner of one of the world’s most admired soccer clubs, FC Barcelona, as well as the jersey partner of NBA Champions, the Golden State Warriors.

Mr. Mikitani was awarded the Legion of Honour by the French government in recognition of contributions to the economy and culture of France. He also serves on the boards of the Tokyo Philharmonic Orchestra and Lyft, Inc. Mr. Mikitani received his B.A. of Commerce at Hitotsubashi University in Tokyo and his MBA at Harvard Business School. At Harvard, he was awarded the Alumni Achievement Award, one of the school’s highest honors.

Prior to his appointment as chief operating officer, Dr. Toraishi led operations as president of Rakuten Aspyrian Japan. Previously he was president of new service development company at Rakuten, Inc., where he spearheaded company-wide innovation initiatives and multiple joint ventures, shared economy and other companies. For nine years, Dr. Toraishi worked with McKinsey & Company, Tokyo, completing his tenure as partner and consultant to global medical device and equipment companies. He started his career as an assistant professor of engineering at the University of Tokyo and led the nuclear chemistry division of the Japan Atomic Energy Agency. Dr. Toraishi received his B.A. of Engineering and his Master of Engineering at the University of Tokyo, his Licentiate of Engineering, Nuclear Chemistry at the Royal Institute of Technology at Stockholm, as well as his Ph.D. in Nuclear Chemistry from the University of Tokyo.