On December 2, 2021 InteRNA Technologies, a clinical-stage biotech company developing microRNA (miRNA)-based therapeutics with a focus on cancer, reported it received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for the company’s Phase I clinical trial evaluating lead miRNA candidate, INT-1B3, in patients with advanced solid tumors (Press release, InteRNA Technologies, DEC 2, 2021, View Source [SID1234596412]). INT-1B3 is a lipid nanoparticle (LNP) formulated, chemically modified mimic of the endogenous tumor suppressor, miR-193a-3p, and represents a promising novel therapeutic approach that is designed to simultaneously address multiple hallmarks of cancer.

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The IND approval enables InteRNA to expand the number of clinical sites and to facilitate the enrollment of patients for the dose expansion (Phase Ib) part of the trial in the United States. The first part of the Phase I trial was initiated in Europe at the beginning of 2021, with the dosing of the first patient in the dose escalation (Phase Ia) part in February. The treatment of the first patient in the Phase Ib cohort is planned for the second half of 2022.

"Receiving such a positive outcome from the FDA shortly after submitting a full IND application is a major achievement for us," commented Laurens van Pinxteren, Chief Operating Officer of InteRNA. "It underlines the high potential of our novel miRNA-based approach that enables us to address the multi-facetted disease cancer from different angles with one drug providing a novel therapeutic entity to patients with hard-to-treat solid tumors, such as advanced breast cancer or hepatocellular carcinoma."

Roel Schaapveld, CEO of InteRNA, added: "The IND approval enables us to enroll an international, diversified patient population, marking significant progress in the clinical evaluation of our novel therapeutic modality. The rapid, positive feedback by the FDA is highly encouraging and we look forward to start patient recruitment in the United States next year."

The multicentric, open-label, multiple ascending dose Phase I/Ib trial (NCT04675996) will investigate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of INT-1B3 in patients with advanced solid tumors. The study is expected to enroll a total of up to 80 patients at up to 15 clinical centers in the United States and Europe. The Phase Ia part of the trial is currently ongoing in the Netherlands and Belgium and will enroll approximately 30 patients with advanced solid tumors. In the second part (Phase Ib) of the trial, approximately 50 patients with hepatocellular carcinoma or triple negative breast cancer will be enrolled in the United States and Europe. Topline results from the Phase Ia part of the study are expected in the first half of 2022.

About INT-1B3

INT-1B3’s unique mechanism of action addresses multiple hallmarks of cancer simultaneously. It directly targets tumor cells and the tumor microenvironment by specific modulation of multiple signaling pathway components across the PTEN tumor suppressor pathway and the oncogenic PI3K/Akt and Ras/MAPK pathways resulting in inhibition of proliferation and migration and induction of cell cycle arrest and apoptosis. The triggering of the immunogenic tumor cell death (ICD) process as well as downregulation of the adenosine-A2A receptor pathway through inhibition of CD39/CD73 leads to a decrease in immunosuppressive FoxP3/Lag3 regulatory T cells and monocytic myeloid-derived suppressor cells (mMDSCs), and maturation of dendritic cells. As a result, the immune system is activated, and long-term immunity is triggered by recruitment of CD8+ effector T cells leading to decreased metastasis development and improved animal survival compared to anti-PD1 treatment.

On December 2, 2021 ITM Isotope Technologies Munich SE, a leading radiopharmaceutical biotech company and Navigo Proteins GmbH, a premier protein engineering company developing optimized scaffold protein-based affinity ligands called Affilin molecules from its Precision Targeting toolbox, reported a research collaboration for the development of a fibroblast activation protein (FAP)-targeted radiopharmaceutical program for the treatment of solid tumors (Press release, ITM Isotopen Technologien Munchen, DEC 2, 2021, View Source [SID1234596411]). The program is planned to be added to ITM’s growing proprietary pipeline of Targeted Radionuclide Therapies spanning multiple radioisotopes and targeting molecules for optimal therapeutic effect. FAP-Targeted Radionuclide Therapy is a promising new approach to treating cancer within the precision oncology field.

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Under the terms of the agreement, Navigo’s proprietary protein engineering platform will be used to develop and select a FAP-targeting Affilin molecule which will then be coupled with a therapeutic radioisotope provided by ITM. Following candidate selection, ITM will have the exclusive rights to further advance the radiolabeled FAP-specific Affilin through clinical testing in potentially multiple cancer indications. The agreement also includes a non-exclusive license for diagnostic use in radio-imaging. Further details of the agreement were not disclosed.

"FAP-targeting approaches have received heightened attention for good reason. We believe this approach holds the potential to treat a wide range of cancer indications. As such, we look forward to exploring this innovative targeted radiopharmaceutical approach for our growing precision oncology pipeline, further expanding its reach and breadth. We believe that developing a new candidate by combining our radioisotopes with an Affilin ligand targeting FAP has the opportunity to make a difference in the lives of patients," commented Steffen Schuster, CEO of ITM.

FAP is a highly attractive tumor target for Targeted Radionuclide Therapy that is preferentially expressed on cancer cells and in particular on cancer associated fibroblasts (CAFs). It is detectable in most epithelial cancers, including over 90% of breast, lung, colorectal and pancreatic carcinomas. High expression levels are associated with poor prognosis, and therefore warrant additional medical research and focus. ITM and Navigo are addressing this urgent need through their research collaboration and combined efforts to develop a promising FAP-targeted radiopharmaceutical.

"We welcome the opportunity to extend our productive partnership with ITM with yet another promising project. We strongly believe in the potential of our technology to generate high-quality Affilin ligands targeting FAP and capable of breaking the tumor microenvironment. By joining forces with ITM, we are fully equipped to build a strong FAP-targeting candidate, that ITM will then advance through clinical development," said Henning Afflerbach, CEO of Navigo Proteins.

The therapeutic candidate developed together by ITM and Navigo will enable a direct attack against tumor cells by irradiating them via crossfire effects in a highly precise manner. Through the direct depletion of CAFs it additionally provides a new access point to modify the tumor microenvironment in which CAFs play a central role in upholding the barrier for effective immune cell infiltration.

This agreement further strengthens the existing partnership between the two organizations, combining ITM’s deep expertise in developing promising Targeted Radionuclide Therapies for cancer patients with Navigo’s proprietary Affilin molecules and protein engineering proficiency.

On December 2, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported that clinical results and updates from its diverse immuno-oncology portfolio will be presented at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress 2021 being held December 8-11, 2021 (Press release, BeiGene, DEC 2, 2021, View Source [SID1234596410]).

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"Despite recent advances in immuno-oncology, chemotherapy remains the standard of care for many patients living with cancer around the world. We look forward to presenting findings on the potential of our anti-PD-1 antibody tislelizumab to treat nasopharyngeal cancer, a rare cancer that is more common in underserved areas of the world, as well as in melanoma and ovarian cancer," commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. "Our R&D team, one of the largest oncology R&D teams in the world, is exploring novel combinations and mechanisms of action around the PD-1 axis to identify potential synergies and overcome PD-1 resistance, as we work to increase access to innovative medicines for patients with limited treatment options."

To learn more about BeiGene’s research and development and activities at ESMO (Free ESMO Whitepaper) IO, please visit View Source

Broad Clinical Program to Address Unmet Needs

To bring forth potential new treatment options and uncover further insights into checkpoint inhibition in solid tumors and hematological malignancies, BeiGene is evaluating tislelizumab, a potentially differentiated anti-PD-1 antibody, in a broad clinical program, including 13 Phase 3 trials and four pivotal Phase 2 trials, and in collaboration with Novartis.

At ESMO (Free ESMO Whitepaper) IO, results from an interim analysis of the randomized, double-blind, Phase 3 RATIONALE 309 trial (NCT03924986) evaluating tislelizumab in combination with chemotherapy in recurrent or metastatic nasopharyngeal cancer (RM-NPC) will be presented in a Proffered Paper. These results supported the regulatory submission in China for NPC.

Novel Combination Therapies to Expand Clinical Benefit of Anti-PD-1 Antibodies

Combination strategy is considered key to overcoming primary and acquired resistance to anti-PD-1 therapy and expanding clinical benefit of immunotherapy to more patients. BeiGene is investigating the potential of novel tislelizumab combinations to drive stronger and more sustained tumor responses and impede tumor immune escape. At ESMO (Free ESMO Whitepaper) IO, results from two cohorts of a Phase 1b trial (NCT03666143) evaluating tislelizumab in combination with the oral, spectrum-selective kinase inhibitor sitravatinib in metastatic melanoma and platinum-resistant ovarian cancer will be presented. BeiGene is developing sitravatinib in collaboration with Mirati Therapeutics, Inc.

Additionally, BeiGene will share details on the design of the Phase 3 AdvanTIG-301 trial (NCT04866017) evaluating its investigational Fc-competent anti-TIGIT-antibody ociperlimab in combination with tislelizumab and concurrent chemoradiotherapy (eCRT) as a first-line treatment for patients with locally advanced, unresectable non-small cell lung cancer.

BeiGene’s Presentations at ESMO (Free ESMO Whitepaper) IO Congress 2021

Presentation Information

Date and Time

Lead Author

121O—RATIONALE 309: A randomized, global, double-blind, Phase 3 trial of tislelizumab versus placebo, plus gemcitabine + cisplatin, as first-line treatment for recurrent/metastatic nasopharyngeal cancer

Proffered Paper Session 2

Fri, Dec 10 at 9 AM CET

Yunpeng Yang

156P—BGB-900-103 Cohort G: Safety/tolerability and antitumor activity of sitravatinib plus tislelizumab in patients with PD-(L)1-refractory/ resistant unresectable or metastatic melanoma from a Phase 1b study

ePoster Display: Therapeutic Development

Thu, Dec 9 at 11:30 AM CET

Chuanliang Cui

153P—BGB-900-103 Cohort E: Safety/tolerability and antitumor activity of sitravatinib plus tislelizumab in patients with advanced platinum-resistant ovarian cancer

ePoster Display: Therapeutic Development

Thu, Dec 9 at 10:30 AM CET

Jeffrey Goh
144P—Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer (TD-NICE): a single arm, phase II study

ePoster Display: Therapeutic Development

Thu, Dec 9 at 7:30 AM CET

Xiaolong Yan

148P—A Phase II Study of tislelizumab plus chemotherapy in EGFR mutated advanced non-squamous NSCLC patients failed to EGFR TKI therapies: first analysis

ePoster Display: Therapeutic Development

Thu, Dec 9 at 8:50 AM CET

Baohui Han

167TiP—AdvanTIG-301: Anti-TIGIT monoclonal antibody ociperlimab plus tislelizumab plus concurrent chemoradiotherapy followed by ociperlimab plus tislelizumab or tislelizumab plus concurrent chemoradiotherapy followed by tislelizumab versus concurrent chemoradiotherapy followed by durvalumab in previously untreated, locally advanced, unresectable non-small cell lung cancer

ePoster Display: Therapeutic Development

Thu, Dec 9 at 3:10 PM CET

Ligang Xing

BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D team of approximately 2,750 colleagues dedicated to advancing more than 70 clinical trials involving more than 14,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 45 countries. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. We currently market three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, Australia and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

On December 2, 2021 NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported that hosted a Key Opinion Leader (KOL) event with Frank A. Giordano, M.D. on November 23, 2021, to discuss the combination of NOX-A12 and radiotherapy in brain cancer (glioblastoma, GBM) (Press release, NOXXON, DEC 2, 2021, View Source [SID1234596409]). Dr. Giordano is Director and Chair of the Department of Radiation Oncology, University Hospital Bonn, Germany, and lead investigator of the ongoing NOX-A12 Phase 1/2 study GLORIA in glioblastoma.

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"I have been involved in research and treatment of glioblastoma for many years, and we’ve not seen major changes in the management of this terrible disease for almost two decades. Although the development of an effective treatment for glioblastoma has proved extremely challenging, the data from the GLORIA study are very promising and, if confirmed in a pivotal clinical study, could be transformational for patients affected by this devastating disease," commented Dr. Frank Giordano.

"Dr. Giordano is a research pioneer and expert in precision radiation therapy and intraoperative irradiation of malignant tumors. He has brought together an exceptional team around the GLORIA study which was evident from the data presentation at SNO. His leadership of the trial will ensure that all the insights we can derive will be put to use in future trials of NOX-A12," commented Aram Mangasarian, CEO of NOXXON.

Glioblastoma is a devastating disease affecting 23,000 new patient each year in the US and Europe. The median overall survival for this patient population is only 14 months, and even lower in the MGMT unmethylated (chemotherapy refractory) patient subpopulation. The KOL webinar highlighted data from the Phase 1/2 GLORIA study presented at the Society for Neuro-Oncology (SNO) Annual Meeting, where tumor shrinkage for patients in the study was significantly stronger compared to those of a historic matched cohort that received standard of care. Eight of 9 MGMT unmethylated glioblastoma patients (89%) receiving NOX-A12 demonstrated tumor size reductions, while only 1 of 13 patients from a matched cohort (8%) showed any tumor shrinkage.

During the KOL event, Dr. Giordano emphasized several other important points, summarized in the Annex to this press release.

On December 2, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the publication of the abstract highlighting interim data, as of a July 14, 2021 cutoff, from the phase 1/2 trial of bispecific antibody MCLA-145 in patients with solid tumors (Press release, Merus, DEC 2, 2021, View Source [SID1234596408]). The e-poster will be presented at the ESMO (Free ESMO Whitepaper) Immuno-Oncology (ESMO IO) Congress 2021 being held December 8-11, 2021 in Geneva, Switzerland.

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Presentation Details:

Title: Phase I Dose Escalation Study of MCLA-145, a Bispecific Antibody Targeting CD137 and PD-L1 in Solid Tumors
Poster #: 136P

The e-poster will be available on the virtual platform, in the e-poster section as of Monday, December 6 at 6:00 am ET and on-site at the e-Poster stations starting on Wednesday, December 8. The poster will also be available on the Merus website.

The phase 1, open-label, single-agent clinical trial of MCLA-145 is ongoing. The trial consists of a dose escalation phase, followed by a planned dose expansion phase. MCLA-145 is the first drug candidate co-developed under Merus’ global collaboration and license agreement with Incyte, which permits the development and commercialization of up to 11 bispecific and monospecific antibodies from the Merus Biclonics platform. Merus retains full rights to develop and commercialize MCLA-145, if approved, in the United States; and Incyte holds full rights to develop and commercialize MCLA-145 outside the United States.

About MCLA-145
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 potential to potently activate immune effector cells in the context of the tumor microenvironment while simultaneously blocking inhibitory signals in the same immune cell population.