On March 14, 2024. Karolinska Development AB (Nasdaq Stockholm: KDEV) reported that its portfolio company Aprea Therapeutics has received FDA approval of the company’s IND application for the drug candidate APR-1051 (Press release, Karolinska Development, MAR 14, 2024, View Source [SID1234641189]). Aprea has also secured funding up to USD 34 million through a financing round led by Sphera Healthcare. With the approval and financing in place, the company will be able to start the first clinical study with APR-1051.

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The American Food and Drug Administration (FDA) has approved Aprea Therapeutics Investigational New Drug (IND) application for the drug candidate APR-1051. APR-1051 is a next-generation inhibitor of Wee1 kinase and the company plans to initiate the clinical phase I study ACESOT-1051. The aim is to evaluate therapeutic activity of APR-1051 in patients, focusing on cancer forms that overexpress Cyclin E, including ovarian and breast cancers.

Aprea Therapeutics has recently conducted a private placement financing of up to USD 34 million that will be used to finance the clinical study. The financing was led by Sphera Healthcare with participation from new and existing healthcare-focused institutional investors including Nantahala Capital, DAFNA Capital Management, Exome Asset Management and Stonepine Capital Management, among others. The financing brings Aprea Therapeutics USD 16 million in up front gross proceeds, with the potential to receive up to an additional USD 18 million.

"The FDA approval and the financial support our portfolio company now receives are clear statements of strength that drive the development of our portfolio company´s innovative drug project forward. We look forward to following the continued development and progress of the company and the project," says Viktor Drvota, CEO Karolinska Development.

Via KDev Investments, Karolinska Development owns 2 percent of the shares in Aprea Therapeutics (before the transaction).

For further information, please contact:

Viktor Drvota, CEO, Karolinska Development AB
Phone: +46 73 982 52 02, e-mail: [email protected]

Johan Dighed, General Counsel and Deputy CEO, Karolinska Development AB
Phone: +46 70 207 48 26, e-mail: [email protected]

On March 14, 2024 Sibylla Biotech reported a drug discovery collaboration with Ono Pharmaceutical Co., Ltd. (TSE: 4528) that will access Sibylla’s cutting-edge Pharmacological Protein Inactivation by Folding Intermediates Targeting (PPI-FIT) technology to identify and develop candidates for multiple therapeutic targets in the field of Central Nervous System (CNS) disorders (Press release, Sibylla Biotech, MAR 14, 2024, View Source [SID1234641188]). Under the terms of the collaboration, Sibylla is entitled to a total deal value in the three-digit millions of U.S. dollars, including upfront payment, research, development and sales milestones, and royalties on sales. Further financial details on the collaboration have not been disclosed.

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"Sibylla’s PPI-FIT technology platform has the potential to surpass the limitations of conventional methods and uncover novel CNS therapeutic targets"

Sibylla Biotech utilizes its PPI-FIT technology to design Folding Interfering Degraders (FIDs). FIDs are small molecules that induce the degradation of a target protein by interfering with its folding pathway. The technology targets specific proteins, particularly those considered "undruggable" due to the absence of suitable pockets in their native state. Ono Pharmaceutical plans to harness this technology to address some of the most challenging aspects of CNS drug development by targeting proteins involved in complex neurological pathways.

"Sibylla’s PPI-FIT technology platform has the potential to surpass the limitations of conventional methods and uncover novel CNS therapeutic targets," said Toichi Takino, Senior Executive Officer/Executive Director, Discovery & Research of Ono Pharmaceutical. "This collaboration is a key part of our strategy to increase efficiency in developing our pipeline in CNS areas and bring innovative solutions to patients facing serious neurological disorders."

"Our partnership with Ono Pharmaceutical represents a fusion of Sibylla’s cutting-edge technology in protein folding simulation with Ono’s extensive experience in CNS research. Together, we aim to unlock new therapeutic possibilities for patients worldwide," commented Lidia Pieri, PhD, Co-Founder and Chief Executive Officer of Sibylla Biotech. "I am honored to collaborate with the Ono Pharmaceutical team, whose rich history, expertise and culture I greatly appreciate, and all of us at Sibylla look forward to working closely with them."

On March 14, 2024 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported that data for its novel, potential first-in-class investigational bispecific antibody, ivonescimab, will be presented at the 2024 European Lung Cancer Congress (ELCC 2024) in Prague, Czech Republic (Press release, Summit Therapeutics, MAR 14, 2024, View Source [SID1234641187]). Two posters featuring updated ivonescimab data will be displayed on Friday, March 22 from 12:00 to 12:45pm Central European Time.

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The first poster, "Intracranial Activity of Ivonescimab Alone or in Combination with Platinum Doublet Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) and Brain Metastases" includes data from patients with asymptomatic brain metastases at baseline. These patients were enrolled in either AK112-202 (NCT04900363), in which ivonescimab is delivered as monotherapy, or AK112-201 (NCT04736823), in which ivonescimab is delivered in combination with platinum doublet chemotherapy, both of which are Phase II clinical trials for patients with advanced or metastatic NSCLC.

The second poster titled, "Phase 2 Results of Ivonescimab a Novel PD-1/VEGF Bispecific in Combination with Chemotherapy for First Line Treatment of Patients with Advanced / Metastatic Squamous Non-Small Cell Lung Cancer" includes updated data from the Phase II trial AK112-201 centered around the cohort of patients in which ivonescimab is combined with chemotherapy for first line treatment of advanced or metastatic NSCLC in patients without actionable genomic alterations (e.g., positive for endothelial growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK)).

The posters will be presented by, amongst others, Dr. Li Zhang, Sun Yat-Sen University Cancer Center, and Dr. H. Jack West, Vice President of Clinical Development at Summit with data generated and analyzed by our collaboration and licensing partner, Akeso Inc. (HKEX Code: 9926.HK), with contribution by Summit staff.

Summit continues its clinical development of ivonescimab in order to establish its efficacy and safety in two NSCLC indications:

HARMONi Phase III trial: ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI)
HARMONi-3 Phase III trial: ivonescimab combined with chemotherapy in first-line metastatic squamous NSCLC patients
About the ELCC 2024 Posters

Poster Title: Phase 2 Results of Ivonescimab a Novel PD-1/VEGF Bispecific in Combination with Chemotherapy for First Line Treatment of Patients with Advanced / Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC)
ELCC Presentation No.: 68P
Session Date & Time: Friday, March 22, 12:00 to 12:45pm CET

Poster Title: Intracranial Activity of Ivonescimab Alone or in Combination with Platinum Doublet Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer and Brain Metastases
ELCC Presentation No.: 174P
Session Date & Time: Friday, March 22, 12:00 to 12:45pm CET

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, is an investigational, novel, potential first-in-class bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays cooperative binding with each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro (Zhong, et al, SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two Phase III clinical trials.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority.

On March 14, 2024 858 Therapeutics reported an upcoming poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, taking place April 5-10 in San Diego, California (Press release, 858 Therapeutics, MAR 14, 2024, View Source [SID1234641186]). The presentation will describe the preclinical characterization of ETX-19477, including potent antitumor activity in multiple animal models.

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Presentation Details for AACR (Free AACR Whitepaper) 2024
Abstract Number: 2083
Title: Discovery of ETX-19477, a novel and selective PARG inhibitor with high potency against tumors with underlying replication stress
Session Title: Novel Targets and Pathways
Session Date and Time: April 8, 2024, 9:00 AM – 12:30 PM (PDT)

About ETX-19477

The company’s lead asset, ETX-19477, is a novel and potent small molecule inhibitor of PARG, a glycohydrolase that plays a pivotal role in the regulation of DNA repair mechanisms and cooperates with PARP to carry out the single-strand break repair cycle. Pharmacological inhibition of PARG results in hyperPARylation, which leads to the death of cancer cells undergoing replication stress. In multiple animal models, ETX-19477 shows potent tumor growth inhibition, and its efficacy is associated with specific biomarker-defined tumors. A Phase I clinical trial is expected to start in the first half of 2024 in patients with advanced solid tumors at multiple sites in the U.S.

On March 14, 2024 Nuvation Bio Inc. (NYSE: NUVB), a biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates, reported that the first patient has been dosed in a Phase 1/2 study of NUV-1511, the Company’s first DDC to enter the clinic (Press release, Nuvation Bio, MAR 14, 2024, View Source [SID1234641185]).

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"Dosing the first patient with NUV-1511 marks a significant milestone for our proprietary DDC platform, from which we are developing potent oncology-focused chimeric small molecules designed to selectively deliver anti-cancer therapeutics to cancer cells, while mitigating effects on healthy non-target tissues," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "DDCs are the core technology upon which the Company was founded and we are excited to bring our first DDC clinical candidate to patients."

The dose escalation portion of the study employs a flexible design that allows for the potential to explore two dosing schedules for NUV-1511 with the goal of establishing the recommended Phase 2 dose. The study will initially evaluate safety and tolerability, pharmacokinetic profile, and assess for signs of clinical activity in patients with advanced solid tumors who previously received and progressed on or after treatment with Enhertu and/or Trodelvy per approved U.S. Food and Drug Administration (FDA) labeling, human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, metastatic castration-resistant prostate cancer (mCRPC), advanced pancreatic cancer, and platinum-resistant ovarian cancer (PROC).