On April 10, 2024 NorthStar Medical Radioisotopes, LLC, a global innovator in development, production and commercialization of radiopharmaceuticals used to detect and treat cancer and other serious diseases, reported the signing of a Clinical Supply Agreement with Clarity Pharmaceuticals for the production of 67Cu-SAR-bisPSMA drug product for Clarity’s Phase I/II and Phase III trials (Press release, NorthStar Medical Radiostopes, APR 10, 2024, View Source [SID1234641998]). The overarching Master Service agreement and associated Clinical Supply Agreement are effective immediately and the initial production of supply to support Clarity trials is expected to occur before the end of calendar 2024.

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"Given Clarity’s outstanding clinical trial data to date, NorthStar is very excited to play a pivotal role in securing the supply of Cu-67 and final drug product for the trials with 67Cu-SAR-bisPSMA in prostate cancer," said Frank Scholz, President and Chief Executive Officer of NorthStar. "We share Clarity’s vision of making more innovative, highly effective radiopharmaceutical treatments available for children and adults with cancer, and our passion is to reduce barriers and increase the speed with which companies like Clarity can develop and deliver these new medicines and diagnostic agents to patients who need them."

Recent years have seen an explosion of radiopharmaceutical research and clinical trials and yet today far too many patients still suffer from diseases without effective treatments. This is partly because the processes to develop, manufacture and deliver effective radiotherapeutics at a scale that meets patient needs are highly specialized and complex, and require a level of process precision above that required by most sophisticated small molecule or biologic manufacturing. Additionally, because the therapeutic nature of these therapies decays at a precise, known rate, there is a level of sophistication required to effectively manage supply chain volatility and uncertainty for radiopharmaceuticals that doesn’t exist for other medicines.

"These unique characteristics and requirements, and the specialized facilities, equipment, processes, talent, technology and know-how that it takes to manufacture and supply radiopharmaceuticals at scale, are what NorthStar does best," continued Scholz. "We are building out our contract development and manufacturing (CDMO) capabilities so that the biopharma innovators like Clarity can focus on discovering the next breakthrough. As we build our business, our goal is for NorthStar to be recognized as a leader in reliable production and delivery of high-quality radiotherapeutics and acknowledged as an essential success factor by our partners."

On April 10, 2024 Opna Bio, a clinical-stage biopharmaceutical company focused on the discovery and development of novel cancer therapeutics, reported promising preclinical data in two programs, OPN-6602, a dual EP300/CBP inhibitor in multiple myeloma, and OPN-9840, an oral, non-covalent TEAD inhibitor in malignant mesothelioma and metastatic melanoma (Press release, Opna Bio, APR 10, 2024, View Source [SID1234641997]). Data were shared at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 5-10, 2024 in San Diego.

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OPN-6602 Significantly Reduced Tumor Growth in Multiple Myeloma Models

OPN-6602 is an orally active, small molecule dual inhibitor of the E1A binding protein p300 (EP300) and CREB-binding protein (CBP) that demonstrated potent in vitro and in vivo anti-tumor activity in preclinical models of multiple myeloma. Multiple myeloma is an aggressive blood cancer derived from malignant plasma cells in the bone marrow.

Significantly reduced tumor growth as single agent (71% tumor growth inhibition, or TGI) in the OPM-2 multiple myeloma cell xenograft model
Demonstrated increased anti-tumor activity (>100% TGI) and sustained duration of response in combination studies with dexamethasone, pomalidomide and mezigdomide
Displayed synergy with dexamethasone and lenalidomide in growth inhibition of MM1.S cells
Showed downregulation of key drivers of the multiple myeloma signaling pathway including MYC, IRF4 and MYB in OPM-2 xenograft tumors
A first-in-human Phase 1 study of OPN-6602 is planned for mid-2024 in patients with multiple myeloma.

"We are excited to begin our Phase 1 study of OPN-6602 in patients with multiple myeloma this summer. While we will study OPN-6602 initially as monotherapy, preclinical data supports testing the compound as a single agent and in combination with standard of care and next generation myeloma therapies," said Jackie Walling, MBChB, PhD, chief medical officer. "The unique pharmacokinetic profile of the compound, with a high c-max and short half-life, in particular, is anticipated to provide a distinct advantage in the combination setting."

OPN-9840 Demonstrated Single Agent Efficacy in Malignant Mesothelioma

OPN-9840 is an oral, non-covalent, pan transcriptional enhanced associate domain (TEAD) inhibitor that demonstrated dose-dependent and on-target in vitro and in vivo efficacy in preclinical models of malignant mesothelioma. Malignant mesothelioma is a rare and aggressive cancer that primarily affects the lining of the lungs or abdomen. In 40% of malignant mesotheliomas, neurofibromatosis 2 (NF2) gene mutations cause dysregulation of the Hippo pathway and increased TEAD-dependent transcription. This aberrant signaling ultimately leads to increased tumor growth and resistance to therapies.

Significantly inhibited tumor growth (88% to >100%) in an NF2-mutant malignant mesothelioma mouse xenograft model. Tumor regression was observed in the 15 mg/kg (2/8 mice) and 50 mg/kg (4/8 mice) dose groups.
OPN-9652, an analog of OPN-9840, showed increased anti-tumor activity (134% TGI) and synergistic inhibition of downstream target genes in a combination study with trametinib
Showed no in vitro cytotoxicity; is well tolerated in vivo while showing potential for blood brain barrier penetration
Additional studies presented through a collaboration with Dr. Andrew Aplin’s laboratory at Thomas Jefferson University demonstrated that Opna TEAD inhibitors enhance BRAF/MEK inhibition in melanoma models by targeting drug-resistant persister cells. Dr. Aplin is a professor in cancer research and deputy director at Jefferson’s NCI-designated Sidney Kimmel Cancer Center.

OPN-9840 is set to begin IND-enabling studies and Opna is currently seeking partnerships for development.

Abstract Information

Title: OPN-6602, a potent dual EP300/CBP bromodomain inhibitor, targets multiple myeloma through concomitant suppression of IRF4 and c-MYC
Abstract Number: #660
Date and time: April 7, 2024; 1:30-5:30 pm PT
Presenter: Bernice Matusow, MS

Title: OPN-9840, a non-covalent potent pan-TEAD inhibitor, exhibits single agent efficacy in preclinical malignant mesothelioma models
Abstract Number: #7264
Date and time: April 10, 2024; 9 am-12:30 pm PT
Presenter: Pan-Yu Chen, PhD

Title: Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models
Abstract Number: #7201
Date and time: April 10, 2024; 9 am-12:30 pm PT
Presenter: Connor Ott, PhD candidate, Thomas Jefferson University

On April 10, 2024 Nuvation Bio Inc. (NYSE: NUVB), a late-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates, reported the completion of the acquisition of AnHeart Therapeutics Ltd. (AnHeart), a late-stage, global biopharmaceutical company developing novel precision therapies for people with cancer (Press release, Nuvation Bio, APR 10, 2024, View Source [SID1234641996]). With the acquisition’s completion, AnHeart is now a wholly-owned subsidiary of Nuvation Bio.

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"The closing of the acquisition transforms Nuvation Bio into a late-stage, global oncology company that is well-capitalized and positioned to develop our newly expanded pipeline as we move toward becoming a commercial organization," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "We welcome the AnHeart team and look forward to leveraging our combined expertise to bring new cancer therapies to patients who need them most."

Nuvation Bio will continue to be led by its current management team, including David Hung, M.D., its Founder, President, and Chief Executive Officer. In addition, Min Cui, Ph.D., Founder and Managing Director of Decheng Capital, an investor in AnHeart, and Junyuan Jerry Wang, Ph.D., Co-Founder and Chief Executive Officer of AnHeart, have joined the Nuvation Bio board of directors.

Following completion of the acquisition, Nuvation Bio issued to the AnHeart security holders, in exchange for all outstanding AnHeart shares, options, and other securities, approximately 43,590,188 shares of Nuvation Bio’s Class A common stock (inclusive of the shares of Class A common stock underlying the AnHeart equity awards assumed by Nuvation Bio), 851,202 shares of Nuvation Bio’s Series A Non-Voting Convertible Preferred Stock (automatically convertible into 85,120,200 shares of Nuvation Bio’s Class A common stock upon the approval of Nuvation Bio’s stockholders), and warrants collectively exercisable for approximately 2,893,731 shares of Nuvation Bio’s Class A common stock at an exercise price of $11.50 per share.

Advisors
Evercore acted as Nuvation Bio’s exclusive financial advisor and Cooley LLP acted as legal counsel, alongside Morrison & Foerster LLP as intellectual property counsel, Haiwen & Partners as Chinese legal counsel, and Conyers as Cayman Islands legal counsel. Davis Polk & Wardwell LLP acted as legal counsel for AnHeart, alongside Fangda Partners as Chinese legal counsel and Walkers (Cayman) LLP as Cayman Islands legal counsel.

On April 10, 2024 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the approval of the CE Mark for the VENTANA HER2 (4B5) Rabbit Monoclonal Primary Antibody RxDx* to identify metastatic breast cancer patients with low HER2 expression for whom ENHERTU (trastuzumab deruxtecan) may be considered as a targeted treatment (Press release, Hoffmann-La Roche, APR 10, 2024, https://www.prnewswire.com/news-releases/roche-obtains-ce-mark-for-first-companion-diagnostic-to-identify-patients-with-her2-low-metastatic-breast-cancer-eligible-for-enhertu-302112437.html [SID1234641995]). The test, which is branded PATHWAY in the United States, received US Food and Drug Administration (FDA) approval in October 2022. ENHERTU is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by Daiichi Sankyo and AstraZeneca.

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HER2 is a receptor protein that helps cancer cells grow quickly. To determine a patient’s HER2 status, pathologists evaluate, or score, the level of HER2 protein expressed in breast cancer tissue samples. If a patient’s tumour expresses high levels of HER2, the patient is identified as HER2-positive and may be considered for HER2-targeted treatment. However, half of all patients with metastatic breast cancer express low levels of HER2 which historically classified them as HER2-negative.

"We are proud to continue our innovation in breast cancer diagnostics through critical tests like this one, which helps identify patients with HER2-low status," said Jill German, Head of Pathology Lab at Roche Diagnostics. "With this expanded approval of our test, we’re pleased that more metastatic breast cancer patients across the world may be correctly identified and potentially eligible for this targeted therapy."

The VENTANA HER2 (4B5) test now includes a scoring algorithm that helps pathologists to identify "low expressors" of HER2, assigning a HER2 low status to this group of patients. With this lower cutoff, the test is able to identify patients who may benefit from ENHERTU as a treatment option.

Breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases diagnosed worldwide each year. More than 685,000 people die from breast cancer every year.4,5

The CE Mark of the new HER2-low indication expands on the intended use for Roche’s proven, on-market VENTANA HER2 (4B5) test, delivering timely, clear and confident results. The launch exemplifies Roche’s commitment to continuing to innovate integrated, high medical value solutions that help to advance personalised healthcare.

About VENTANA HER2 (4B5) Rabbit Monoclonal Primary Antibody RxDx
Roche’s pre-diluted VENTANA HER2 (4B5) Rabbit Monoclonal Primary Antibody RxDx, used in combination with the fully automated BenchMark IHC/ISH slide staining instrument, standardises all immunohistochemistry (IHC) processes from baking through staining, and reduces the possibility of human error.5 It also minimises inherent variability resulting from individual reagent dilution and other processes found in manual and semi-automated IHC methods. The Roche HER2 (4B5) clone achieves consistently high proficiency assessment scores compared to other clones6 and demonstrates high concordance with HER2 FISH7,8, empowering laboratories to employ the most widely adopted and reliable HER2-IHC primary antibody.

The VENTANA HER2 (4B5) test was used as part of the DESTINY-Breast04 trial to identify patients whose tumours expressed low levels of HER2 protein (IHC 1+ or IHC 2+/ISH-). The trial reported a 50% reduction in the risk of disease progression or death and an overall survival gain of six months over standard of care in patients treated with ENHERTU whose tumours had low levels of HER2 expression, leading to the approval of ENHERTU in this patient population.

On April 10, 2024 Compugen Ltd. (NASDAQ: CGEN) (TASE: CGEN) a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported the simultaneous online publication of a peer reviewed paper titled ‘Unleashing natural IL-18 activity using an anti-IL-18BP blocker antibody induces potent immune stimulation and anti-tumor effects’ link, in Cancer Immunology Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) with a presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting on April 5-11, 2024, in San Diego, California (Press release, Compugen, APR 10, 2024, View Source [SID1234641994]).

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"There is a growing recognition of the importance of the IL-18 pathway in cancer immunology reflected in the surge in investment and collaboration in this space," said Anat Cohen-Dayag, Ph.D., President, and Chief Executive Officer of Compugen. "Through our computational discovery work at Compugen we identified that IL-18 binding protein (BP), a natural inhibitor of IL-18, is highly expressed in patients as a potential immune resistant mechanism. Taking advantage of the high levels of endogenous IL-18BP bound-IL-18 in the tumor microenvironment, we, along with our partner Gilead Sciences are developing COM503, a differentiated antibody approach to harness cytokine biology for cancer therapeutics."

Eran Ophir, Ph.D., Chief Scientific Officer at Compugen added, "Our paper published online yesterday in Cancer Immunology Research describes how COM503, a potential first-in-class high affinity monoclonal antibody, blocks the interaction between IL-18 and IL-18BP, unleashing the activity of endogenous IL-18 in the tumor. By relying on endogenous production of IL-18, we found that COM503’s activity is localized to the tumor microenvironment with the additional advantage of a wider therapeutic window than systemic IL-18 delivery."

Dr. Cohen-Dayag continued, "Combining the cutting-edge capabilities and expertise of both Compugen and Gilead, our goal is to expedite the development of COM503. This year, we are progressing towards COM503 IND filing and are planning initiation of a Phase 1 study evaluating safety and tolerability of COM503."