On June 21, 2024 BCI Pharma reported that the company has been acquired by Gedeon Richter (Press release, BCI Pharma, JUN 21, 2024, View Source [SID1234644488]).

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Dominique Surleraux, former BCI Pharma CEO, said : "This acquisition will ensure the continuity and development of the BCI and also further clinical development of our assets/research projects. I would like to take the opportunity to thank BCI scientists for their input, BCI investors and the Belgium Walloon region Ministry of economic (SPW wallonie) for their financial support. I’m pretty confident that our assets will improve the quality of life of patients suffering from cancer and endometriosis."

On June 21, 2024 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported new preclinical data from its investigational BCL6 PROTAC degrader ARV-393 at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Annual Congress that took place June 13-16, 2024 in Madrid, Spain, and presented new preclinical data from its PROTAC LRRK2 degrader program at the Biennial International LRRK2 Meeting that took place June 18-21, 2024 in Crete, Greece (Press release, Arvinas, JUN 21, 2024, View Source [SID1234644487]).

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Data presented at EHA (Free EHA Whitepaper) showed anti-tumor activity for the company’s investigational PROTAC BCL6 degrader, ARV-393, in preclinical models of B-cell lymphoma. In these preclinical models, ARV-393 potently and rapidly degraded the BCL6 protein and inhibited cell growth in diffuse large B-cell lymphoma (DLBCL) and Burkitt cell lines. ARV-393 showed tumor growth inhibition, including tumor regression, in various DLBCL cell line-derived xenograft (CDX) models and in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL), including germinal center B-cell-like (GCB), activated B-cell (ABC), GCB/ABC, BCL not otherwise specified (BCL/NOS) subtypes of DLBCL, and Burkitt lymphoma.

"These new preclinical data for ARV-393 demonstrate that in these models it can effectively target and induce the degradation of the BCL6 protein that is commonly deregulated in DLBCL," said John Houston, Ph.D., Chairperson, President, and Chief Executive Officer at Arvinas. "These encouraging results suggest that ARV-393 could be developed into a potential new treatment for patients with certain types of non-Hodgkin lymphoma, particularly those who have not responded to other treatments."

Preclinical data presented at the Biennial LRRK2 Meeting highlighted the potential of the company’s oral PROTAC LRRK2 degraders to treat neurodegenerative diseases. Preclinical studies in mice demonstrated full target engagement of LRRK2 kinase inhibitor and near-complete LRRK2 degradation with PROTAC LRRK2 degraders, but substantially less Type II pneumocyte enlargement compared to an experimental LRRK2 kinase inhibitor. In addition, the more noticeable Type II pneumocyte enlargement phenotype observed with the experimental LRRK2 kinase inhibitor was substantiated by the accumulation of surfactant protein C in lung, which was not observed after treatment with a PROTAC LRRK2 degrader.

"Nonclinical findings presented this week suggest the potential for a wide therapeutic index and manageable safety profile for PROTAC degraders versus experimental LRRK2 kinase inhibitors," said Angela Cacace, Ph.D., Chief Scientific Officer at Arvinas. "In earlier preclinical studies, Arvinas’ PROTAC LRRK2 degraders have been shown to cross the blood-brain barrier and degrade LRRK2, a large multidomain scaffolding kinase, in deep brain regions."

Arvinas’ oral PROTAC BCL6 degrader ARV-393 is currently in a phase 1 clinical trial in patients with NHL, and Arvinas also has an oral PROTAC LRRK2 degrader, ARV-102, currently being investigated in a phase 1 clinical trial in healthy volunteers.

About ARV-393

ARV-393 is an investigational PROTAC designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response. PROTAC-mediated degradation has the potential to address the traditional undruggable nature of BCL6. ARV-393 is currently in a phase 1 clinical trial in patients with non-Hodgkin lymphoma.

About ARV-102

ARV-102 is an investigational PROTAC designed to degrade Leucine-rich repeat kinase 2 (LRRK2) which is a large multidomain scaffolding kinase. Human genetics, increased activity and expressions of LRRK2 is genetically involved in the pathogenesis of neurological diseases including Parkinson’s Disease and progressive supranuclear palsy. Arvinas is developing oral, blood-brain-barrier penetrant PROTAC degraders of LRRK2.

On June 21, 2024 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported that it will host a virtual KOL event to discuss APR-1051, a highly selective and potentially best-in-class oral WEE1 inhibitor, on Monday, June 24, 2024 at 9:00 AM ET (Press release, Aprea, JUN 21, 2024, View Source [SID1234644482]). To register, click here.

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The webinar will feature Joseph Vacca, PhD, Medicinal Chemistry Expert and Consultant to Aprea, who will discuss the medicinal chemistry history, highly selective drug design, and preclinical findings of APR-1051. It will also feature Eric J. Brown, PhD (University of Pennsylvania) who will discuss preclinical findings across the WEE1 inhibitor class. WEE1 is an enzyme involved in the DNA damage response pathway and is a validated oncology target.

APR-1051 is a potent and selective small molecule that has been designed to limit off-target toxicity. Aprea recently initiated the Phase 1 ACESOT-1051 trial evaluating APR-1051 as monotherapy treatment in patients with significant unmet medical need, including patients with Cyclin E over expression.

A live question and answer session will follow the formal presentations.

Joseph Vacca, PhD is a medicinal chemist who spent 30 years at Merck Research Laboratories (1981 to 2011). He and his teams made major contributions to several approved drugs including the HIV protease inhibitor CRIXIVAN (indinavir sulfate), the HIV integrase inhibitor Isentress (raltegravir); the HCV protease Inhibitor (Vanihep, vaniprevir), the combination product Zepatier which is a combination of the second generation HCV protease Inhibitor grazoprevir and the NS5A protein Inhibitor elbasvir and the recently approved second generation HIV NNRTI inhibitor doravirine. Upon his retirement from Merck in 2011, Dr. Vacca took a role as Senior Vice President of Early Success Sharing Partnerships at WuXi AppTec Limited. He left WuXi in September 2015 to be a consultant and now acts as an interim head of chemistry for several small startup companies. Dr. Vacca has over 100 publications and patents and is the holder of many awards including a Merck Directors Award (1998); PhRMA Discoverers Award (1999); Intellectual Property Owners "National Inventor of the year Award" (1997); European Inventor of the Year (non-EU nation) (2007); ACS "Award for Creative Invention" (1999); and was a named a Merck Research Laboratories Presidential Fellow in 2008. He was named to the American Chemical Society Medicinal Chemistry Hall of Fame (Aug. 2012) and was also named a "Hero of Chemistry" (along with the research team) for his role in the discovery and development of the HIV integrase inhibitorIsentress. Dr. Vacca earned a BS in chemistry in 1977 from St. John Fisher College, Rochester, New York, and obtained a PhD degree in Organic Chemistry under Professor Peter T. Lansbury Sr. at the State University of New York at Buffalo (New York).

Eric J. Brown, PhD is Associate Professor of Cancer Biology at the University of Pennsylvania and a Scientific Consultant to Aprea Therapeutics. Dr. Brown’s laboratory at Penn focuses on the role of the replication stress response on genome stability. His research seeks to identify the cancer-associated genetic changes that increase the efficacy of therapeutics that abrogate replication stress responses, such as ATR and WEE1 inhibitors. The genetic changes that impact sensitivity to these therapies are identified through various orthogonal approaches, including proteomics, genome-wide breakpoint mapping, and computational methods. Overall, the goal of this research is both to better understand the mechanism by which these cancer therapeutics operate and to improve responses to these treatments in patients.

On June 21, 2024 Nerviano Medical Sciences S.r.l. ("NMS" or the "Company"), a part of NMS Group S.p.A. (NMS Group) and Nerviano Medical Sciences, Inc., a wholly owned subsidiary of NMS Group, focused on the discovery and development of oncology drugs and the largest oncological R&D company in Italy, reported the strategic discontinuation of three development programs to further prioritize and reinforce efforts on core programs (Press release, Nerviano Medical Sciences, JUN 21, 2024, View Source [SID1234644481]).

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NMS-088, a next-generation, clinical-stage FLT3 inhibitor. The decision is the result of internal analysis of the benefit profile of the drug in the third line (3L) setting in patients who are refractory or relapsed after standard of care including prior FLT3 inhibitors and considering the further development in rapidly changing AML treatments. NMS will report the data in in the first half of 2025;
NMS-173, a potent covalent orally available, second-generation dual IDH1/ IDH2 inhibitor, inducing abrogation of 2-HG production and anti-tumor efficacy in IDH mutant mouse models superior to competitors, thus suggesting potential for better efficacy in patients compared to available drugs. NMS-173 has received authorization to start phase I studies in US and Europe for the treatment of patients with IDH1 and IDH2 mutated solid tumors, including cholangiocarcinoma;
NMS-341, a late preclinical-stage next-generation inhibitor of CDC7, with potential for Best-in- Class, due to its unique combination of potency on target, cross-reactivity to CDK9 and oral bioavailability. Based on its broad efficacy as single agent and in combination, and in view of CDC7 role in DNA-damage response, NMS-341 can be used to treat patients with a wide range of solid and hematological tumors, also in combination with chemotherapy and as radio-ligand sensitizer.
NMS is open for potential collaborations or partnerships around these assets, with the right partners to maximize the value of these trusted programs.

NMS remains committed to discover and develop innovative therapies able to address unmet medical needs in oncological patients and will continue to invest to strengthen a focused, high-impact portfolio.

On June 21, 2024 HUTCHMED (China) Limited ("HUTCHMED") reported that its partner Takeda has received notification from the European Commission ("EC") that it has approved FRUZAQLA (fruquintinib) as a monotherapy indicated for the treatment of adult patients with metastatic colorectal cancer ("CRC") who have been previously treated with available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents, and who have progressed on or are intolerant to treatment with either trifluridine-tipiracil or regorafenib (Press release, Hutchison China MediTech, JUN 21, 2024, View Source [SID1234644480]).

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"With fruquintinib being the first and only selective inhibitor of all three VEGFRs to be approved in the EU for colorectal cancer, this decision represents a significant milestone in European oncology," added Josep Tabernero, MD, PhD, director of Vall d´Hebron Institute of Oncology (VHIO). "There is a clear need in Europe for patients and their clinicians to be able to access a new treatment option for previously treated metastatic colorectal cancer, and we are excited that this important step has been taken so that we can begin prescribing this new and differentiated medicine."

"We are delighted to have achieved EC approval for FRUZAQLA and that we can now offer a new therapeutic option for patients with previously treated metastatic colorectal cancer, regardless of their biomarker status," said Teresa Bitetti, President of the Global Oncology Business Unit at Takeda. "Patients in Europe with metastatic colorectal cancer have long needed additional treatment options, and we are grateful to be able to meet that need thanks to our partnership with HUTCHMED."

"This is a significant milestone for HUTCHMED, as it is the first product from our research and discovery engine to be approved in Europe, achieved through our partnership with Takeda to make this possible in such a short period of time," added Weiguo Su, PhD, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. "This novel oncology medicine is currently improving the treatment outlook in the U.S. and China, and we look forward to seeing its impact for patients across Europe."

The EC’s approval has been granted following a positive opinion from the Committee for Medicinal Products for Human Use ("CHMP") in April 2024. The CHMP’s opinion was primarily based on results from the Phase III multiregional FRESCO-2 trial, which supported the Marketing Authorisation Application ("MAA") that was validated and accepted for review in June 2023. Data from FRESCO-2 were published in The Lancet in June 2023.

About CRC
CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer/World Health Organization, CRC is the third most prevalent cancer worldwide, associated with more than 1.9 million new cases and 900,000 deaths in 2022. In Europe, CRC was the second most common cancer in 2022, with approximately 538,000 new cases and 248,000 deaths.[1],[2] In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.[3] In Japan, CRC was the most common cancer, with an estimated 146,000 new cases and 60,000 deaths, in 2022.[2] Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.[4],[5],[6],[7],[8]

About the Phase III FRESCO-2 Trial
FRESCO-2 is a multiregional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus best supportive care ("BSC") versus placebo plus BSC in patients with previously treated metastatic CRC (NCT04322539). FRESCO-2 met all of its primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS), with consistent benefit among patients treated with fruquintinib, regardless of the prior types of therapies they received. Fruquintinib demonstrated a manageable safety profile in FRESCO-2, consistent with previously reported fruquintinib monotherapy studies. Adverse reactions leading to treatment discontinuation occurred in 20% of patients treated with fruquintinib plus BSC versus 21% of those treated with placebo plus BSC. Results from the study were presented at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) in September 2022 and subsequently published in The Lancet in June 2023.[9],[10]

About Fruquintinib
Fruquintinib is a selective oral inhibitor of all three VEG receptors (VEGFR‑1, ‑2 and ‑3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off‑target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for its potential use as part of a combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti‑cancer therapies.

About Fruquintinib Approval in China
Fruquintinib is approved for marketing in China, where it is co‑marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approval was based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic colorectal cancer in China, which were published in The Journal of the American Medical Association, JAMA. Since its launch in China and as of mid‑2023, more than 80,000 patients with colorectal cancer have been treated with fruquintinib.