On April 12, 2022 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a private, clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, reported that the first patient has been dosed in the Company’s Phase 1 clinical trial of IO-202, a first-in-class myeloid checkpoint inhibitor targeting Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4, also known as ILT3) for the treatment of patients with advanced solid tumors (NCT05309187) (Press release, Immune-Onc Therapeutics, APR 12, 2022, View Source [SID1234612095]).

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"We are very pleased to announce the initiation of our Phase 1 study of IO-202 in solid tumors, a significant achievement in our development strategy targeting the LILRB family of myeloid checkpoints to overcome immune suppression in the tumor microenvironment," said Paul Woodard, M.D., chief medical officer of Immune-Onc. "We believe by targeting the LILRB4 checkpoint, IO-202 may reverse the immunosuppressive effects of tumor associated monocytic myeloid cells, enhance dendritic cell function, and promote T cell activation – thereby, unleashing the antitumor activities of the immune system and increasing the therapeutic benefit of T cell checkpoint inhibitors. We look forward to conducting this study and assessing the potential of IO-202 as a monotherapy and in combination with pembrolizumab across multiple solid tumor types."

This study consists of two parts: a dose escalation portion to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IO-202 alone and in combination with pembrolizumab, an anti-PD-1; and a dose expansion portion using the recommended Phase 2 dose of IO-202 in combination with pembrolizumab in multiple solid tumor types. Various biomarkers will be explored to enable a mechanistic understanding of clinical data and inform future trials. This study may also provide an opportunity to identify preliminary efficacy signals for IO-202 as a monotherapy and as a combination with a PD-1 inhibitor in patients with advanced solid tumors.

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune inhibitory transmembrane receptor expressed by monocytic myeloid cells, including dendritic cells, monocytes, monocytic myeloid-derived suppressor cells and tumor-associated macrophages. LILRB4 inhibits antigen-presenting cell function, resulting in immune tolerance. LILRB4 is also expressed on certain hematologic cancer cells. Immune-Onc and The University of Texas published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in acute myeloid leukemia (AML) and presented the rationale for targeting LILRB4 in solid tumors at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

ABOUT IO-202

IO-202 is a first-in-class LILRB4 antagonist antibody with broad potential as an immunotherapy in both blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells. In the context of solid tumors, preclinical studies showed that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in an immune competent model in vivo.

IO-202 has two ongoing clinical studies: Its first Phase 1 trial is currently enrolling patients with acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML) as a monotherapy and in combination with azacitidine (NCT04372433). The U.S. Food and Drug Administration granted IO-202 Orphan Drug designation for treatment of AML in 2020 and Fast Track designation for relapsed or refractory AML in 2022. The second Phase 1 trial of IO-202 is currently enrolling patients with advanced solid tumors to evaluate IO-202 as a monotherapy and in combination with an anti-PD-1 (NCT05309187).

On April 12, 2022 Lysogene (FR0013233475 – LYS) (Paris:LYS), a phase 3 gene therapy platform Company targeting central nervous system (CNS) diseases, reported that it has exercised its option to enter into an exclusive worldwide license agreement with Yeda Research and Development Co Ltd, the commercial arm of the Weizmann Institute of Science, for the development and commercialization of a gene therapy candidate for the treatment of neuronopathic Gaucher disease and Parkinson disease (PD) with GBA1 mutations (Press release, Lysogene, APR 12, 2022, View Source [SID1234612094]).

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Since 2020, Lysogene has been collaborating with Prof. Anthony Futerman at the Weizmann Institute of Science with the aim of developing a novel AAV gene therapy approach for neuronopathic Gaucher disease, Parkinson disease, and other diseases associated with mutations of the GBA1 gene. Lysogene has provided expertise in AAV vector design and production, while Prof. Futerman’s lab provided glucocerebrosidase variants with enhanced biological properties. After approximately 20 months of successful collaboration, Lysogene decided to exercise its option to license the program on the basis of positive preliminary biological proof of principle studies.

Under the terms of the agreement, Lysogene will be responsible for the preclinical and clinical development, manufacturing, regulatory activities, and commercialization of the drug candidate, globally. Yeda Research and Development Co Ltd will be eligible for royalties and other payments.

Ralph Laufer, CSO of Lysogene, commented: "We are thrilled to add to our R&D pipeline a new promising gene therapy asset, which addresses high unmet medical needs in Gaucher disease, as well as broader indications, such as PD-GBA. The first results obtained by Prof. Anthony Futerman’s team are promising and we look forward to expanding them in additional preclinical studies. The cost of these preclinical studies will not affect our cash runway. We continue to replenish our early-stage pipeline to position Lysogene as a key player in the field of gene therapy translational science."

"We are excited to expand our successful research collaboration with Lysogene based on the novel research by Prof. Futerman and his colleagues," said Elik Chapnik, Sr. Director of Business Development at Yeda. "We are confident that this new licensing deal has the potential to bring transformative therapeutic options to patients suffering from genetically-defined CNS diseases with significant unmet need, such as neuronopathic Gaucher disease."

On April 12, 2022 Chimeron Bio, an RNA company developing self-amplifying RNA (saRNA) vaccines and therapeutics designed on its proprietary ChaESAR RNA delivery platform, reported it has entered into a manufacturing agreement with FUJIFILM Diosynth Biotechnologies (FDB), a leading Contract Development and Manufacturing Organization (CDMO) with experience in the development and manufacture of recombinant biopharmaceuticals and viral gene therapies, to advance the Company’s Oncology portfolio to the clinic (Press release, Chimeron Bio, APR 12, 2022, View Source [SID1234612092]).

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Chimeron Bio selected FUJIFILM Diosynth Biotechnologies as its partner for the transfer and scale up of their drug substance manufacturing process. Drug substance manufacturing will be carried out in FUJIFILM Diosynth Biotechnologies’ state-of-the-art cGMP manufacturing facility in College Station, Texas. Materials from this partnership will help facilitate Chimeron’s IND-enabling work and entry into the clinic.

"We selected FUJIFILM Diosynth Biotechnologies as our manufacturing partner because of their proven track record in the advanced therapies space," said Jolly Mazumdar, chief executive officer, Chimeron Bio. "FDB really understands our ChaESAR platform and pipeline potential, making them the best partner to scale up our processes and help bring our ground-breaking approach for the treatment of underserved patients closer to reality."

"Chimeron’s ChaESAR platform has the potential to impact how we bring treatments and therapies to patients," said Gerry Farrell, chief operating officer, FUJIFILM Diosynth Biotechnologies, Texas site. "We are delighted to be the partner of choice to bring their technology into our GMP facility and produce Bulk Drug Substance to support their clinical trials."

About Chimeron’s ChaESAR platform

The ChaESAR platform is a self-assembling biosynthetic non-lipid nanoparticle (NLNP) comprising a self-amplifying RNA genome encased within a capsid with a surface ligand of choice.

On April 12, 2022 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported the publication of its study titled, "A machine learning algorithm with subclonal sensitivity reveals widespread pan-cancer human leukocyte antigen loss of heterozygosity," in Nature Communications (Press release, Personalis, APR 12, 2022, View Source [SID1234612091]).

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Human leukocyte antigen loss of heterozygosity (HLA LOH) allows cancer cells to escape immune recognition by deleting HLA alleles, causing the suppressed presentation of tumor neoantigens. Despite its importance in immunotherapy response, few methods exist to detect HLA LOH, and their accuracy is not well understood. Further, detecting HLA LOH accurately from sequencing data is of interest given the growing ubiquity of tumor molecular profiling.

The Personalis study details the development of DASH (Deletion of Allele-Specific HLAs), a novel machine learning-based algorithm to detect HLA LOH from paired tumor-normal sequencing data. Through validation with cell line mixtures and patient-specific digital PCR, the study demonstrates increased sensitivity of HLA LOH detection by DASH compared to previously published tools and paves the way for clinical utility. Using DASH for 610 patients across 15 tumor types, the study found that a large percentage of patients are impacted by HLA LOH, including patients with non-small cell lung cancer adenocarcinoma (NSCLC-A) (24 percent), cervical cancer (38 percent), and head and neck squamous cell carcinomas (HNSCC) (40 percent). Additionally, the study showed inflated HLA LOH rates compared to genome-wide LOH, and correlations between CD274 (PD-L1) expression and microsatellite instability status, suggesting that HLA LOH is a key immune resistance strategy.

"Accurate detection of HLA LOH is critical for its use as a biomarker for cancer immunotherapy. This study demonstrates DASH’s ability to sensitively detect subclonal events in samples with low tumor purity, enabling comprehensive profiling of widespread HLA LOH across tumor types," said Richard Chen, MD, chief medical officer and SVP of R&D for Personalis. "Integrated with Personalis’ NeXT Platform, these DASH-identified HLA LOH events are a key input to our composite, multi-omic biomarker, NEOPS, to better predict immunotherapy response."

On April 12, 2022 Radionetics Oncology, a pharmaceutical company focused on the discovery and development of novel radiotherapeutics for the treatment of a wide range of oncology indications, reported the appointment of Nishan de Silva, M.D. as its Chief Executive Officer (Press release, Radionetics Oncology, APR 12, 2022, View Source [SID1234612089]). Dr. de Silva brings more than 20 years of experience in biotechnology operations, biopharmaceutical venture capital and healthcare consulting to Radionetics and joins a veteran leadership team leveraging a broadly enabling platform to expand the application of radiopharmaceuticals.

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The company’s technology platform uses small molecule targeting to deliver therapeutic radioisotopes to a broad range of cancers by binding selectively to peptide receptors that are overexpressed on many tumors. This platform has the potential to be impactful in nearly all solid tumors and Radionetics is rapidly advancing multiple candidates with the expectation of filing three INDs in the next two years.

"Nishan’s rich experience building companies, coupled with Radionetics’ deep scientific and drug development expertise, gives the company an ability to mobilize its robust technology platform to rapidly develop targeted small molecule radiopharmaceuticals in pursuit of precision treatments for cancer," said Scott Struthers, Ph.D., Chairman of Radionetics. "We are delighted to have Nishan take the helm and accelerate the company’s momentum in this exciting field of oncology therapeutics."

"Radionetics is pursuing a differentiated approach in an emerging therapeutic class that has the potential to upend current standards of care in radiation oncology," said Dr. de Silva. "The company’s focus on pursuing novel oncology targets using a small molecule approach with a platform that is agnostic to the type of radioisotope is very attractive. In addition, recent scientific advancements and significant improvements in the radiopharmaceutical supply chain are unlocking vast opportunities to deliver precise and powerful radiopharmaceuticals to patients as well as meaningful financial returns for investors. The strength of the Radionetics team and platform uniquely position the company for success and I’m excited to take on this leadership role."

During his career, Dr. de Silva has built multiple companies, bringing novel pharmaceuticals through financing and clinical development. Prior to joining Radionetics, Dr. de Silva was the CEO at AFYX Therapeutics where he led a successful Phase 2 clinical trial program for a first-ever sponsor-conducted study in oral lichen planus. He also raised the financing to enable the achievement of that key value creating milestone and led the development and implementation of new IP strategies to ensure the program’s exclusivity position. Before AFYX Therapeutics, Dr. de Silva served as President and Chief Operating Officer for Poseida Therapeutics, a leading gene therapy and gene editing therapeutics-focused company. There, he oversaw clinical, regulatory, technical operations, finance, business development and human resources functions through direct reporting relationships. Dr. de Silva played a key leadership role in raising over $100 million in capital, and he oversaw the advancement of the company’s lead asset from preclinical concept through successful establishment of clinical proof-of-concept in a Phase 1/2 clinical trial in multiple myeloma.

Dr. de Silva holds a B.A. summa cum laude in biology from Harvard University, an M.D. from The University of Pennsylvania School of Medicine and an M.B.A. with Distinction in healthcare management from The Wharton School.

Dr. de Silva joins the founding Radionetics management team, which includes Yu-Fei (Frank) Zhu, Ph.D., Deborah Slee, Ph.D., Brett Ewald, Ph.D., and Ana Kusnetzow, Ph.D. In addition to his CEO role, he will serve as a director on the company’s board. Since launching in October 2021, Radionetics has added eight new members to the team and plans to more than double over the coming year.