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Xencor Regains ex-U.S. Commercial Rights to XmAb®13676, CD20 x CD3 Bispecific Antibody

On January 7, 2019 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic disease and cancer, reported it will regain rights to develop and commercialize XmAb13676, a CD20 x CD3 bispecific antibody, from Novartis effective June 20, 2019, due to strategic pipeline reprioritization by Novartis (Press release, Xencor, JAN 7, 2019, View Source [SID1234532562]). Xencor granted Novartis co-development and ex-U.S. commercial rights in June 2016 through a collaboration and license agreement to develop and commercialize novel bispecific antibodies, including XmAb13676 and XmAb14045, and to access Xencor’s XmAb bispecific Fc and other Fc technologies. Currently XmAb13676 is being evaluated in an open-label Phase 1, multiple-dose, dose-escalation study to assess its safety, tolerability and preliminary anti-tumor activity in patients with B-cell malignancies, and initial data are expected in 2019.

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"We continue to work closely with Novartis across multiple programs in the collaboration, and both companies are eager to advance XmAb14045 in clinical development. Recently we presented encouraging early data from our Phase 1 study in patients with relapsed/refractory AML, observing multiple complete remissions on a weekly dosing schedule, and we continue to optimize dose in that study. Novartis also has internal XmAb preclinical bispecific programs progressing," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Xencor will continue to develop XmAb13676 as planned, and we believe its tuned potency holds potential for the treatment of patients with B-cell malignancies."

Under the terms of the collaboration agreement, Xencor and Novartis continue to share costs for the worldwide development of XmAb14045 with Xencor maintaining U.S. commercialization rights and Novartis having commercialization rights in the rest of the world, and worldwide development costs for XmAb13676 will be shared until June 2020. Novartis received worldwide rights to Xencor’s bispecific technology to develop and commercialize four additional targets selected by Novartis. Xencor is eligible to receive clinical, regulatory and sales milestone payments for successful programs, as well as tiered, low double-digit royalties for sales of XmAb14045 outside of the U.S. and mid single-digit tiered royalties for worldwide sales of the four proprietary Novartis bispecific molecules.

About XmAb13676

XmAb13676 is a tumor-targeted antibody that contains both a CD20 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of B-cell malignancies. An XmAb bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb13676. CD20 is highly expressed on B-cell tumors, including in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Engagement of CD3 by XmAb13676 activates T cells for highly potent and targeted killing of CD20-expressing tumor cells.

About XmAb14045

XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

Sanofi and Regeneron Restructure Immuno-Oncology Collaboration for Discovery and Development Programs

On January 7, 2019 Sanofi (EURONEXT: SAN, NASDAQ: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that they have restructured their global Immuno-oncology Discovery and Development Agreement for new immuno-oncology cancer treatments (Press release, Sanofi, JAN 7, 2019, View Source [SID1234532561]). The 2015 Agreement was scheduled to end in approximately mid-2020, and this revision provides for ongoing collaborative development of two clinical-stage bispecific antibody programs. This provides Sanofi increased flexibility to advance its early-stage immuno-oncology pipeline independently while Regeneron retains all rights to its other immuno-oncology discovery and development programs.

Under the terms of the restructured Agreement:

Sanofi will pay Regeneron $462 million representing the balance of payments due under the original Immuno-oncology Agreement, which covers the Sanofi share of the immuno-oncology discovery program costs for the last quarter of 2018 and up to $120 million in development costs for the two selected clinical-stage bispecific antibodies, plus the termination fee for the other programs under the original immuno-oncology agreement.
Sanofi secures the right to opt-in to the BCMAxCD3 and MUC16xCD3 bispecific programs when proof of concept is achieved or when the allocated funding is expended.
Regeneron will commit up to $70 million to further develop the BCMAxCD3 bispecific antibody for multiple myeloma and up to $50 million to further develop the MUC16xCD3 bispecific for mucin-16 expressing cancers.
Post opt-in, Sanofi will lead development and commercialization of the BCMAxCD3 bispecific and fund 100 percent of development costs, with Regeneron reimbursing up to 50 percent out of its share of collaboration profits. Sanofi and Regeneron will share global profits equally.
Post-opt-in, Regeneron will lead MUC16xCD3 bispecific development and lead commercialization in the U.S. The companies will share development costs and global profits equally. Sanofi will lead commercialization outside the U.S.
The companies’ ongoing collaboration for the development and commercialization of Libtayo (cemiplimab-rwlc), a PD1 antibody, is unaffected by the amended Discovery and Development Agreement.
Regeneron retains full rights to its other immuno-oncology programs.
Under the Immuno-Oncology License and Collaboration Agreement, the companies have developed and received U.S. Food and Drug Administration approval of Libtayo for advanced cutaneous squamous cell carcinoma (CSCC). A regulatory application for Libtayo has also been submitted in the EU. An ongoing joint clinical program is investigating Libtayo in multiple other cancers, and includes potentially pivotal trials in lung, cervical and skin cancers. Libtayo’s safety and efficacy has not been fully evaluated by any regulatory authority for indications beyond advanced CSCC.

Merus Announces IND Clearance for MCLA-145

On January 7, 2019 Merus N.V. (Nasdaq: MRUS), a clinical-stage immuno-oncology company developing Biclonics, innovative full-length human bispecific antibody therapeutics, reported the U.S. Food and Drug Administration (FDA) has accepted the Investigational New Drug (IND) application for MCLA-145, a first-in-class PD-L1 x CD137 Biclonics being developed in collaboration with Incyte (Nasdaq: INCY), for the treatment of solid tumors (Press release, Merus, JAN 7, 2019, View Source;p=RssLanding&cat=news&id=2382290 [SID1234532560]).

"We are pleased to announce the IND authorization to proceed from the FDA and to disclose more details around our latest Biclonics program today," said Andres Sirulnik, M.D., Ph. D., Executive Vice President and Chief Medical Officer of Merus. "Our preclinical work has demonstrated that MCLA-145 has the potential to overcome the known side effects of CD137 agonists currently in development and to address a significant unmet need in patient populations not benefitting from current immunotherapeutic agents. We expect to initiate the clinical trial program for MCLA-145 during the second quarter of 2019 and we look forward to continuing our collaboration with Incyte on MCLA-145’s global development."

Discovered through an unbiased functional screening of multiple immunomodulatory target combinations, MCLA-145 is a Biclonics T-cell agonist that binds with high affinity and specificity to human PD-L1 and CD137 in preclinical models. The unique immunostimulatory profile of MCLA-145 derives from the ability to potently activate immune effector cells in the context of the tumor microenvironment while simultaneously blocking inhibitory signals in the same immune cell population.

Merus is developing MCLA-145 as part of a collaboration entered into with Incyte in December 2016 to potentially develop and commercialize up to 11 bispecific and monospecific antibodies from the Merus Biclonics platform. Under the terms of the collaboration, Merus will retain all rights to develop and commercialize MCLA-145, if approved, in the United States, while Incyte has rights to develop and commercialize MCLA-145, if approved, outside the United States.

Epigenomics AG Announces Positive Results from Microsimulation Model

On January 7, 2019 Epigenomics AG (FSE: ECX, OTCQX: EPGNY) reported that a microsimulation model has been completed by external academic experts demonstrating positive results for the Epi proColon blood test (Press release, Epigenomics, JAN 7, 2019, View Source [SID1234532559]). The manuscript is being finalized and will be submitted for publication soon. Epigenomics will discuss the specific findings once the manuscript is published.

Microsimulation models have been used to project the harms and benefits of various strategies for Colorectal Cancer Screening (CRC). These models are utilized by various screening guideline groups such as the United States Preventative Services Task Force (USPSTF) and the American Cancer Society to aid in the development of screening guidelines. To date, none of the previously completed models used for guideline development have incorporated the methylated Septin 9 blood test (Epi proColon) as one of the strategies. The model just completed incorporates the Epi proColon test and also factors in the key variable of adherence to testing. Adherence to testing is a critical element for the improvement of screening rates, and blood based testing holds promise for the approximately 35% of eligible people not up to date for screening according to the guidelines.

Nanobiotix and MD Anderson Cancer Center announce a large-scale, comprehensive clinical collaboration on NBTXR3

On January 7, 2019 NANOBIOTIX (Euronext : NANO – ISIN : FR0011341205) and The University of Texas MD Anderson Cancer Center reported a large-scale, comprehensive clinical research collaboration to evaluate innovative strategies for treating patients with head and neck, pancreatic, thoracic, lung, gastrointestinal and genitourinary cancers (Press release, Nanobiotix, JAN 7, 2019, View Source [SID1234532558]).

The collaboration will expand clinicaldevelopment of NBTXR3, a first-in-class agent designed to physically destroy cancer cells when activated by radiotherapy and to activate the immune system for both local control and systemic disease treatment.

MD Anderson will initially conductthe launch of nine new phase I/II clinical trials-involving around 340 patients-focused on evaluating the potential clinical benefit of NBTXR3 when activated by radiotherapy, either as a monotherapy or in combination with checkpoint inhibitors. The planned trials also will look at various disease stages, including low-risk/good prognostic patients, locally advanced disease, and metastatic disease. The trials will studyNBTXR3 across different radiation modalities such as radiation, re-irradiation, and compare different levels of intensity of radiation, to evaluate whether the addition of NBTXR3 to radiotherapy will improve progression-free survival, loco-regional control, quality of life and organ preservation.

Dr. Thomas Morris, Global Head of Development, Nanobiotix, said "It is important for Nanobiotix to collaborate with academic institutionsto develop a broad spectrum of clinical trials in an expedited fashion. This is a tremendous opportunity to strengthen our scientific and clinical understanding of the potential of NBTXR3 across the wide range of cancers treated with radiotherapy, with the goal of benefitting patients by applying novel research and bringing forward an innovative therapy. The collaboration between Nanobiotix and MD Anderson expands the number of NBTXR3 clinical trials to 16, illustrating our dedication to identify more effective treatments for cancer patients.

As part of the funding scheme for this collaboration, part of the payment will be made at the start of the collaboration. Other parts will be paid during development and the balance in case of FDA registration for a total of $12M investment.

This new collaboration between Nanobiotix and MD Anderson follows up the immunotherapeutic pre-clinical research collaboration, launched in April 2018, in lung cancer to explore NBTXR3 potential in immuno-oncology with checkpoint inhibitors, as well as its potential to control metastatic disease.

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.

NBTXR3 is a late clinical stage product which has shown the potential for clinical benefit in advanced STS phase III randomized clinical trial.

NBTXR3 is actively being evaluated in head and neck cancer with locally advanced squamous cell carcinoma of the oral cavity or 2 oropharynx in elderly and frail patients unable to receive chemotherapy. The other ongoing studies 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.

Nanobiotix is also running an Immuno-Oncology development program. In the U.S., the Company received the FDA’s approval 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).