On January 13, 2025 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, FLAMINGO-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences, reported the activation of clinical sites in France (Press release, Greenwich LifeSciences, JAN 13, 2025, View Source [SID1234649658]).

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According to the latest data collected by the European Cancer Information System (click here), a total of 66,328 new cases of breast cancer were diagnosed in France in 2022, which is the most common cancer diagnosed in women, representing approximately 33% of all cancers in women. Breast cancer is the leading cause of death from cancer in women in France with 14,739 deaths in 2022.

The Company has partnered with Unicancer and its breast cancer group (UCBG), the largest academic breast cancer research network in France. The FLAMINGO-01 study will be activated in approximately 19 French sites in the UCBG network. These sites were approved by French authorities in Q1 2024, which led to site initiation visits and training of 15 sites in Q2-Q4 of 2024, with the remaining 4 sites scheduled for start-up activities in Q1-Q2 of 2025.

Unicancer is the only hospital network in France entirely dedicated to the fight against cancer and the only national hospital federation dedicated to oncology. It brings together 18 Cancer Centers (CLCC), non-profit private healthcare institutions, spread across 20 hospital sites in France, along with two affiliated member institutions. The CLCCs care for nearly 530,000 patients annually (in short-stay, home hospitalization, and outpatient care). Unicancer is also the leading academic sponsor of clinical trials in oncology on a European scale, with 106 active clinical trials sponsored in 2020 and nearly 7,600 patients enrolled. Unicancer also leads flagship programs that enable the use of real-world data to improve the understanding and evaluation of therapeutic strategies, particularly through the ESME platforms, which gather data from over 76,000 cancer patients. Recognized as a leader in research in France, the Unicancer network enjoys a global reputation, contributing to a third of the internationally significant French publications in oncology (source: bibliometric study/Thomson Reuters).

In total, nearly 700 clinical trials (enrollment or follow-up) were sponsored by the Unicancer network in 2020, with over 14% of CLCC patients participating in clinical trials and more than half of the PHRCs (hospital clinical research programs) dedicated to the CLCCs. The 18 CLCCs and the R&D department of Unicancer are ISO 9001:2015 certified for their clinical research. More information on Unicancer can be found at View Source

UCBG develops clinical trials within its network of more than 100 investigating centers covering the whole of France and all types of institutions (University Hospitals, General Hospitals, Comprehensive Cancer Centers, private institutions) to allow wide access to ongoing studies. The UCBG is an internationally recognized intergroup, labeled by the INCa (national cancer institute), and is the preferred contact for the development of studies on breast cancer in France. The UCBG collaborates with the ARCAGY-GINECO intergroup to further increase its network and consolidate its role as a privileged academic interlocutor in France.

"Major work to improve patient care has been carried out and published by the UCBG. Participation in the FLAMINGO study will allow us to stay at the forefront of clinical research in the domain of vaccination against cancer" said Dr. T. Bachelot, President of the UCBG.

Dr. F.C. Bidard, who serves on the FLAMINGO-01 Steering Committee and is the national Principal Investigator for France for FLAMINGO-01 commented, "Anti-tumor vaccines are becoming more and more attractive in addition to standard treatments. GLSI-100 mechanism of action is orthogonal to that of both chemotherapy and anti-HER2 targeted therapies and holds the promise to improve the outcome of patients at high risk of relapse."

Dr. Bidard is a Medical Oncologist and Head of Breast Cancer Group at Institut Curie in Paris and Professor of Medicine at Versailles University. Dr. Bidard has developed several key trials investigating new biomarkers and new therapeutic approaches in breast cancer. Since 2023, he has also served as the Vice-Chair of UCBG.

Jaye Thompson, VP of Clinical and Regulatory Affairs, added "Collaboration with Unicancer allows the Company the opportunity to offer FLAMINGO-01 to patients in France in an efficient manner, reaching all the large population centers in France. I have attended many of the initiation visits and am very impressed with the interest level and professionalism of these leading cancer institutes in France."

CEO Snehal Patel commented, "When we first met Dr. Bidard, he had some proposals for additional clinical trials for GLSI-100 while we were still planning the start-up of the Phase III trial. This relationship eventually led to a partnership with Unicancer to bring Flamingo-01 to the major hospitals in France. We also invited Dr. Biddard to participate on our Steering Committee and are grateful for his guidance and support over the years."

The 19 Unicancer clinical sites are listed on clinicaltrials.gov with an interactive map and are shown below.

Avignon

Sainte-Catherine – Institut du Cancer Avignon-Provence (ICAP)

Beauvais

Centre Hospitalier Simone Veil de Beauvais

Brest

Clinique Pasteur-Lanroze

Caen

Centre François Baclesse (CLCC)

Clermont-Ferrand

Pôle Santé République – ELSAN

Guilherand-Granges

Hôpital privé Drôme Ardèche

Lyon

Centre Léon Bérard

Nice

Centre Antoine Lacassagne

Osny

Centre Hospitalier Privé Sainte-Marie Osny

Paris

Institut Curie

Pontoise

Hôpital NOVO (Nord-Ouest Val-d’Oise)

Quimper

Centre Hospitalier Intercommunal de Cornouaille Quimper Concarneau (CHIC)

Reims

Institut Godinot (CLCC)

Saint-Cloud

Institut Curie

Saint-Grégoire

Centre Hospitalier Privé Saint-Grégoire

Saint-Priest-en-Jarez

Centre Hospitalier Universitaire de Saint-Étienne

Strasbourg

Institut de cancérologie Strasbourg Europe

Vantoux

Hôpital Robert Schuman

Villejuif

Institut Gustave Roussy

About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2 positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US clinical sites from university-based hospitals and cooperative networks with plans to expand into Europe and to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on FLAMINGO-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 300,000 new breast cancer patients and 4 million breast cancer survivors. HER2 (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On January 13, 2025 GSK plc (LSE/NYSE: GSK) and IDRx, Inc. (IDRx) reported that they have entered into an agreement under which GSK will acquire IDRx, a Boston-based, clinical-stage biopharmaceutical company dedicated to developing precision therapeutics for the treatment of GIST (Press release, GlaxoSmithKline, JAN 13, 2025, View Source [SID1234649657]). Under the agreement, GSK will pay $1 billion upfront, with potential for an additional $150 million success-based regulatory approval milestone payment. The acquisition includes lead molecule, IDRX-42, a highly selective KIT TKI being developed as a first- and second-line therapy for the treatment of GIST.

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GIST typically presents in the GI tract with 80% of cases driven by mutations in the KIT gene that lead to the growth, proliferation, and survival of tumour cells (primary or activating mutations).1 90% of patients treated in the first-line develop new KIT mutations (secondary or resistance mutations) that typically lead to relapse with limited therapeutic options.2 Currently, there are no approved TKIs that inhibit the full spectrum of clinically relevant primary and secondary mutations in KIT.

IDRX-42 has demonstrated activity against all key primary and secondary KIT mutations, designed to improve outcomes for patients with GIST. This breadth of mutational coverage, in addition to high selectivity which could improve tolerability, provides potential for a best-in-class profile.

Luke Miels, Chief Commercial Officer, GSK, said: "IDRX-42 complements our growing portfolio in gastrointestinal cancers. This acquisition is consistent with our approach of acquiring assets that address validated targets and where there is clear unmet medical need, despite existing approved products."

Tony Wood, Chief Scientific Officer, GSK, said: "We are excited by the early data from IDRX-42 and its unique ability to target all clinically relevant KIT mutations present in GIST, a major gap in the current standard of care. We look forward to accelerating its development in 2025 to redefine treatment."

Updated clinical data from StrateGIST 1, an ongoing phase I/Ib trial of IDRX-42 in patients with advanced GIST, were presented in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting. These data show promising anti-tumour activity of IDRX-42 in patients with advanced GIST with a manageable safety profile. Across patients with second-line or greater GIST, and amongst all KIT mutation subsets, the objective response rate (ORR) by modified RECIST v1.1 in the total efficacy evaluable population was 29% (n=87), including one complete response (CR) and 24 partial responses (PRs). Amongst patients who have had one prior line of therapy, the ORR was 53% (n=15) including one CR and 7 PRs.3

Across all patients, two of the PRs were awaiting confirmation at the time of the data cut, both of which were subsequently confirmed. The emerging durability data from StrateGIST 1 was also favourable. IDRX-42 was generally well-tolerated and treatment-related adverse events (TRAEs) were mainly low grade at the recommended phase Ib dose.4

Tim Clackson, CEO, IDRx, said: "We are looking forward to working with GSK to advance IDRX-42 for patients with GIST given there have been no major advances to the standard of care for almost 20 years. Combining our experience to date with GSK’s expertise in GI cancers, global clinical development capability, and strong commercial presence in oncology will help to accelerate the development of this novel medicine for patients."

GSK has a growing portfolio in development targeting the significant medical need in GI cancers, including ongoing trials with dostarlimab and GSK5764227 (GSK’227), a B7-H3-targeted antibody-drug conjugate. This agreement reflects GSK’s portfolio approach of identifying potentially best-in-class molecules with targeted mechanisms of action. The transaction supports GSK’s ambitions for growth through 2031 and beyond.

Financial considerations
Under the terms of the agreement, GSK will acquire one hundred percent (100%) of the outstanding equity interests (including all options and other incentive equity) in IDRx for up to $1.15 billion of total cash consideration, comprising an upfront payment of $1 billion with potential for an additional $150 million success-based regulatory approval milestone payment. GSK will also be responsible for success-based milestone payments as well as tiered royalties for IDRX-42 owed to Merck KGaA, Darmstadt, Germany.

This transaction is subject to customary conditions, including applicable regulatory agency clearances under the Hart-Scott-Rodino Act in the US.

For IDRx, Centerview Partners LLC is acting as exclusive financial advisor and Goodwin Procter LLP as legal counsel. For GSK, Leerink Partners LLC is acting as the exclusive financial advisor.

About GIST
Gastrointestinal stromal tumours (GIST) are the most common subtype of soft tissue sarcoma, with about 80,000 to 120,000 patients diagnosed with GIST per year worldwide.5 GIST typically presents in the GI tract with 80% of cases driven by mutations in the KIT gene that lead to the growth, proliferation, and survival of tumour cells (primary or activating mutations in exons 9 and 11).6 Additionally, about 90% of patients treated in the first-line develop new KIT mutations (secondary or resistance mutations in exons 13 and 17) that typically lead to relapse with limited therapeutic options.7 There are no approved TKIs that inhibit the full spectrum of clinically relevant primary and secondary mutations in KIT.

About IDRX-42
IDRX-42 is a highly selective, investigational small molecule tyrosine kinase inhibitor (TKI) designed to target all key KIT mutations in GIST. The U.S. Food and Drug Administration (FDA) has granted IDRX-42 Fast Track designation for the treatment of patients with GIST after disease progression on or intolerance to imatinib, and Orphan Drug designations for the treatment of GIST.

On January 13, 2025 Genprex presented its corporate presentation (Press release, Genprex, JAN 13, 2025, View Source [SID1234649656]).

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On January 13, 2025 Galectin therapeutics presented its corporate presentation (Presentation, Galectin Therapeutics, JAN 13, 2025, View Source [SID1234649655]).

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On January 13, 2025 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, reported its strategic objectives for 2025 (Press release, Foghorn Therapeutics, JAN 13, 2025, View Source [SID1234649654]).

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"In 2025, we expect important progress across our inhibitor and degrader programs. Our highly selective SMARCA2 inhibitor, FHD-909, continues to enroll and dose patients in a Phase 1 trial for SMARCA4 mutated cancers, with NSCLC as the primary patient population. In addition, for FHD-909, preclinical combination data with pembrolizumab and KRAS inhibitors will be presented at the AACR (Free AACR Whitepaper) Annual Meeting in April, with partner Lilly," said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. "We are also excited with the progress of our preclinical pipeline. We have successfully achieved selective degradation of ARID1B, a major synthetic lethal target implicated in up to 5% of all solid tumors, and plan to provide a program update in 2025. We are continuing to advance our Selective CBP degrader and our Selective EP300 degrader, which are both implicated in a wide range of cancers. With our strong balance sheet and pipeline programs advancing, we look forward to an impactful 2025."

*Unaudited, estimated as of December 31, 2024

Program Overview and Upcoming Milestones

FHD-909 (LY4050784). FHD-909 is a first-in-class oral SMARCA2 selective inhibitor that has demonstrated in preclinical studies to have high selectivity over its closely related paralog SMARCA4, two proteins that are the catalytic engines across all forms of the BAF complex. Selectively blocking SMARCA2 activity is a promising synthetic lethal strategy intended to induce tumor death while sparing healthy cells. SMARCA4 is mutated in up to 10% of NSCLC alone and implicated in a significant number of solid tumors.
•Advancing Phase 1 trial. First patient dosed in October 2024 in the Phase 1 trial for FHD-909 in SMARCA4 mutated cancers, with NSCLC as the primary target population.
•Preclinical combination data to be presented. In 2025, preclinical data for FHD-909 in combination with pembrolizumab or KRAS inhibitors will be presented at the AACR (Free AACR Whitepaper) Annual Meeting (April 25-30, 2025).

Ongoing strategic collaboration with Lilly. Collaborating with Lilly to create novel oncology medicines that includes a U.S. 50/50 co-development and co-commercialization agreement for Foghorn’s selective SMARCA2 oncology program, agreements for a selective inhibitor and a selective degrader, and an additional undisclosed oncology target. The collaboration also includes three discovery programs from Foghorn’s proprietary Gene Traffic Control platform.

Selective CBP degrader program. Selectively targets CBP in EP300 mutated cancer cells found in many types of cancer, including bladder, gastric and endometrial cancers. CBP and EP300 are highly similar acetyltransferases that create a synthetic lethal relationship when EP300 is mutated. Attempts to selectively drug CBP have been challenging due to the high level of similarity between the two proteins, while dual inhibition of CBP/EP300 has been limited by hematopoietic toxicity.
•Identified potent and selective CBP protein degraders. Pharmacodynamic and pharmacokinetic preclinical data demonstrate:
oDeep and sustained CBP degradation significantly inhibited tumor growth in mouse xenograft solid tumor models.
oRobust monotherapy preclinical anti-tumor activity that was not associated with significant body weight loss, thrombocytopenia or anemia.
oLong-acting injection formulation that resulted in tumor regression from a single dose in a mouse xenograft efficacy study.

Selective EP300 degrader program. Selective degradation of EP300 for the treatment of hematopoietic malignancies and prostate cancer. Attempts to selectively drug EP300 have been challenging due to the high level of similarity between EP300 and CBP, while dual inhibition of CBP/EP300 has been limited by hematopoietic toxicity. EP300 lineage dependencies are established in multiple myeloma, and diffuse large B cell lymphoma.

•Identified potent and selective EP300 degraders and advancing oral degrader efforts. Pharmacodynamic and pharmacokinetic preclinical data demonstrate candidates:
oAre well tolerated in vivo with no observed decrease in platelet levels, and no effects on megakaryocyte viability at pharmacologically relevant concentrations in ex vivo studies.
oHave robust anti-tumor activity in solid tumors and hematological malignancies, including prostate cancer, multiple myeloma, and diffuse large B cell lymphoma.

Selective ARID1B degrader program. Selectively targets and degrades ARID1B in ARID1A-mutated cancers. ARID1A is the most mutated subunit in the BAF complex and amongst the most mutated proteins in cancer. These mutations lead to a dependency on ARID1B in several types of cancer, including ovarian, endometrial, colorectal and bladder. Attempts to selectively drug ARID1B have been challenging because of the high degree of similarity between ARID1A and ARID1B and the fact that ARID1B has no enzymatic activity to target.
•ARID1B is a major synthetic lethal target implicated in up to 5% of all solid tumors.
•Developed highly potent and selective binders. Preclinical data demonstrated potent and selective small molecule binders to ARID1B.
•Selective degradation of ARID1B achieved. Foghorn has successfully selectively degraded ARID1B and expects to provide an update on the Selective ARID1B degrader program in 2025.

Chromatin Biology and Degrader Platform
Foghorn continues to advance its chromatin biology and degrader platform with investments in novel ligases, long-acting injectables, oral delivery and induced proximity.

Strong Balance Sheet and Cash Runway. As of December 31, 2024, the Company had $243.8 million cash, cash equivalents and marketable securities (unaudited), providing cash runway into 2027.