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.

On April 12, 2022 OncoNano Medicine, Inc. reported positive results from the company’s ON-BOARD pH-sensitive nanoparticle platform (Press release, OncoNano Medicine, APR 12, 2022, View Source [SID1234612088]). The data, presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, demonstrate that the clinically validated ON-BOARD platform has the potential to be a universal tool for tumor specific activation and the efficient delivery of proteins for an improved therapeutic index.

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"Our ON-BOARD micelle platform is designed to efficiently carry a broad range of payloads to the tumor microenvironment. Capable of being tuned to deliver either small molecules or biologics, the ON-BOARD platform has the potential to be a universal tool for targeted delivery of therapeutics to a range of cancers," said Tian Zhao, Ph.D., Vice President of Research & Development for OncoNano Medicine, Inc. "We are pleased with the positive data from our research efforts to encapsulate therapeutic antibodies with our ON-BOARD delivery technology and look forward to the further development of protein payloads with an improved therapeutic index."

A variety of biosimilar monoclonal antibodies including those of atezolizumab, cetuximab, pembrolizumab, trastuzumab and ipilimumab were encapsulated by the ON-BOARD platform. The findings indicate that ON-BOARD demonstrated:

Encapsulation of antibodies without additional modification of the original antibody
Encapsulation efficiency ranging from 50-100%
Formulations characterized as uniformly distributed particles < 100nm in size with good stability
Over a 100-fold activation window between the acid-activated and intact formulations based on in vitro assessment by cell-based reporter assays
pH-dependent activation that was further confirmed by affinity and binding assay
Tumor specific accumulation that was demonstrated by a biodistribution study
Presentation Overview

TITLE:
Encapsulating therapeutic antibodies for tumor specific activation and delivery using a clinically validated pH-sensitive nanoparticle platform

PRESENTER:
Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine

On April 12, 2022 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported the issuance of a key US Patent related to its industry-leading minimal residual disease (MRD) and recurrence platform, NeXT Personal (Press release, Personalis, APR 12, 2022, View Source [SID1234612087]).

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The patent, US Patent No. 11,299,783, entitled "Methods and Systems for Genetic Analysis," was issued on April 12, 2022. The ‘783 patent claims novel methods for a partially personalized assay, combining both tumor-informed and prespecified (tumor naïve) content. Tumor-informed methods can provide high sensitivity for detection of MRD. They can also support tracking of variants specific to an individual patient’s cancer, such as those targeted by specific therapies or which are thought to elicit an immune response. Prespecified, tumor-naïve content can include variants not detected on initial sequencing of a tumor, but which may emerge and confer drug resistance as a tumor evolves. It can also include driver mutations of a second primary tumor, which may arise independently during the course of the initial cancer. The ‘783 patent is a member of a patent family that broadly describes Personalis’ foundational work relating to the development of personalized assays for disease identification and tracking.

Personalis’ recently introduced NeXT Personal platform leverages many elements of the ‘783 patent. It is unique among MRD assays in that it combines a highly sensitive measurement of tumor burden with simultaneous tracking of thousands of tumor variants, both tumor-informed and prespecified, in a single panel design.

The issuance of the ‘783 patent adds to Personalis’ growing intellectual property portfolio that includes multiple early families related to personalized genetic testing. Overall, Personalis has 19 issued US and foreign patents, spanning 16 distinct families, relating to advanced genomic sequencing and analysis solutions. In addition, the company has over 25 pending US and foreign patent applications that relate to its existing advanced cancer detection platforms and novel research areas, including methods for interpreting genetic data generated by its platforms.

"Cancer is very complex and dynamic," said John West, CEO and co-founder of Personalis. "Our NeXT Personal approach combines detection, quantification, and detailed characterization of a patient’s tumor in a single, integrated data stream. As the cost and turnaround time of both DNA sequencing and DNA synthesis have rapidly improved, sensitive and detailed monitoring over a patient’s entire clinical trajectory has become affordable, and we believe that it will become the new standard of care."

On April 12, 2022 Blue Earth Therapeutics, a Bracco company and emerging leader in the development of innovative next generation therapeutic radiopharmaceuticals, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug Application (IND) application for 177Lu-rhPSMA-10.1 (Press release, Blue Earth Therapeutics, APR 12, 2022, View Source [SID1234612085]). IND authorization to proceed enables Blue Earth Therapeutics to initiate a Phase 1/2 clinical study to evaluate the safety, tolerability, dosimetry and anti-tumor activity of 177Lu-rhPSMA-10.1 in men with metastatic castrate-resistant prostate cancer (mCRPC). 177Lu-rhPSMA-10.1 is the first clinical candidate in Blue Earth Therapeutics’ oncology development program of next generation therapeutic radiopharmaceuticals. Blue Earth Therapeutics holds exclusive worldwide rights to therapeutic applications of radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) radiopharmaceutical technology to help advance the treatment of patients with prostate cancer.

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"Clearance to proceed with this first clinical study for 177Lu-rhPSMA-10.1 marks an exciting milestone for our new company, Blue Earth Therapeutics, and the patients with cancer that we hope to serve," said David E. Gauden, D.Phil., Chief Executive Officer of the Company. "We consider 177Lu-rhPSMA-10.1 to be a next generation PSMA therapy with the potential to be best-in-class. 177Lu-rhPSMA-10.1 is the result of a careful optimization process which aimed to maximize therapeutic index by delivering high radiation doses to prostate cancer lesions while sparing normal tissues wherever possible. Excitingly, this optimized technology can be developed with both beta- and alpha-emitting therapeutic radioisotopes. We look forward initially to applying our proven radiopharmaceutical development expertise in advancing 177Lu-rhPSMA-10.1, and, over time, developing a pipeline of additional oncology therapeutics to help address significant unmet patient needs."

The trial is an open-label, multi-center, integrated Phase 1 and 2 study to evaluate the safety, tolerability, radiation dosimetry and anti-tumor activity of 177Lu-rhPSMA-10.1 in men with metastatic castrate-resistant prostate cancer. Phase 1 will investigate the safety, tolerability and dosimetry of multiple cycles of 177Lu-rhPSMA-10.1 in subjects with PSMA-positive mCRPC which has progressed following prior therapy. Results from Phase 1 will be used to determine the recommended treatment regimen to be tested in Phase 2. The Phase 1 study will be conducted at clinical sites in the United States, with further sites added for the Phase 2 component of the trial, in both the United States and Europe.

About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

rhPSMA compounds are referred to as radiohybrid ("rh"), as each molecule possesses three distinct domains. The first consists of a Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells. It is attached to two labelling moieties which may be radiolabeled with either 18F for PET imaging, or with isotopes such as 177Lu or 225Ac for therapeutic use – creating a true theranostic technology. They may play an important role in patient management in the future, and offer the potential for precision medicine for men with prostate cancer. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Therapeutics and Blue Earth Diagnostics work closely on the development of 177Lu-rhPSMA-10.1. Currently, rhPSMA compounds have not received regulatory approval.

On April 12, 2022 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported that new preclinical data from its Wee1 inhibitor program in a poster session at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in New Orleans (Press release, Schrodinger, APR 12, 2022, View Source [SID1234612084]). Schrödinger has identified multiple, highly selective and structurally distinct Wee1 inhibitors with optimized physicochemical properties that show strong pharmacodynamic responses and anti-tumor activity in preclinical models. The data presented show that Schrödinger’s Wee1 inhibitors have therapeutic potential for use as monotherapy and as part of combination therapy with other agents.

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"The strength of our data underscore the potential of our novel, orally available and potent Wee1 inhibitors and provide an opportunity to advance a potential best-in-class Wee1 inhibitor into the clinic," said Karen Akinsanya, Ph.D., president of R&D, therapeutics, at Schrödinger. "The differentiated and balanced profile of our Wee1 molecules highlights the impact of our computational platform when deployed at scale to overcome design challenges, such as selectivity and ADME optimization. Our unique lead series were identified by assessing more than 445 million potential compounds computationally with only 42 that were synthesized for further analysis."

Wee1 is a gatekeeper checkpoint kinase that prevents cellular progression through the cell cycle, allowing time for DNA repair before cell division takes place. Inhibition of Wee1 allows for accumulation of DNA damage, triggering DNA breakage and apoptosis in tumor cells. Wee1 is emerging as a potentially important therapeutic target for a range of solid tumors, including ovarian and uterine cancer.

Schrödinger is on track to select a Wee1 development candidate later this year. Subject to completion of the preclinical data packages, Schrödinger anticipates submitting an Investigation New Drug (IND) Application to the U.S. Food and Drug Administration (FDA) in 2023.

Additional Details About the Study
The presentation, "Discovery of potent, selective, and orally available Wee1 inhibitors that demonstrate increased DNA damage and mitosis in tumor cells leading to tumor regression in vivo," highlighted preclinical data with multiple lead compounds discovered using Schrödinger’s proprietary physics-based free energy perturbation (FEP+) modeling technology. These molecules demonstrate superior kinase selectivity compared to other known Wee1 inhibitors in a broad kinase panel. In multiple preclinical models, a representative compound, STC-8123, was well tolerated and demonstrated sustained pharmacodynamic and pharmacokinetic properties. The anti-tumor effects of STC-8123 were maintained during dosing holidays while allowing full recovery of mechanism-based hematological effects, likely due to its sustained plasma concentrations and high exposure in tumors. Schrödinger’s advanced Wee1 program compounds maintained potency, selectivity and anti-tumor activity with no detectable time-dependent inhibition of CYP3A4, a key liver enzyme. Taken together, these data support a profile that may enable a favorable dosing regimen and further evaluation of a potential best-in-class Wee1 inhibitor as both monotherapy and as part of combination therapy with other agents.