On February 20, 2024 Treadwell Therapeutics, a privately held clinical-stage biotechnology company pioneering and advancing novel first-in-class medicines for unmet needs in cancer, reported the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to ocifisertib (CFI-400945), a first-in-class, investigational PLK4 inhibitor for the treatment of acute myeloid leukemia (AML) (Press release, Treadwell Therapeutics, FEB 20, 2024, View Source [SID1234640293]). Ocifisertib is currently being evaluated in a Phase 1b/2 study in adults with relapsed/refractory AML following standard of care therapy.

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Orphan drug designation is granted by the FDA to drugs intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the U.S. at the time of designation. Under the FDA’s Orphan Drug Act, orphan drug status provides incentives, grants, tax credits and waiver of certain administrative fees as well as seven years of market exclusivity following marketing authorization.

Treadwell also announced today the appointment of Brenda Marczi, as SVP and Head of Regulatory Affairs. Brenda comes to Treadwell with over 30 years of regulatory experience in the pharmaceutical and biotechnology industries. She most recently served as Senior Vice President, Regulatory Affairs at Tracon Pharmaceuticals, Inc., where she oversaw their regulatory function and led all of their strategies and filing activities in the US and UK. Brenda holds a Master of Science in Pharmaceutical Sciences from Rutgers University, a PharmD from the University of Maryland, and an MBA from Wharton, University of Pennsylvania.

"The FDA’s decision to grant orphan drug designation, along with the previous FDA Fast Track designation for ocifisertib underscores Treadwell’s dedication to addressing this patient population with few treatment options. Patients with relapsed and/or refractory AML, in particular TP53 mutated disease suffer poor overall survival and represents a high unmet clinical need," said Roger Sidhu, M.D., Acting CEO of Treadwell. "We look forward to advancing ocifisertib in partnership with investigators, regulators, patients and their families for those with limited treatment options in tough to treat AML. In addition, we are thrilled to have Brenda join us to lead Regulatory Affairs at Treadwell. She is a seasoned strategic leader with a broad experience in leading regulatory strategy from early development through approval. Her leadership will be invaluable to Treadwell as we advance ocifisertib into potentially pivotal studies in 2025."

On February 20, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported the publication of a peer-reviewed article in Frontiers in Immunology that enhances understanding of the molecular mechanism of action of sudocetaxel zendusortide (also known as TH1902) as a potential anticancer treatment (Press release, Theratechnologies, FEB 20, 2024, View Source [SID1234640291]). Sudocetaxel zendusortide is an investigational, first-in-class peptide-drug conjugate (PDC) that targets the sortilin receptor (SORT1) and expedites the internalization and delivery of the cytotoxic payload (docetaxel) directly into cancer cells.

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The article, "Sudocetaxel Zendusortide (TH1902) triggers the cGAS/STING pathway and potentiates anti-PD-L1 immune-mediated tumor cell killing" appears in the "Cancer Immunity and Immunotherapy" section of the February (Volume 15) issue of the journal. It reports on preclinical research in which sudocetaxel zendusortide induced complete and prolonged tumor regression in a triple-negative breast cancer (TNBC)-derived xenograft tumor model and demonstrated tumor regression associated with growth inhibition and immune cell infiltration in a "cold" murine (syngeneic) tumor model. Additionally, combining sudocetaxel zendusortide with an anti-PD-L1 checkpoint inhibitor led to increases in tumor growth inhibition and median animal survival.

"The results published in Frontiers in Immunology demonstrate that sudocetaxel zendusortide exerts its antitumor activity, in part, through modulation of the immune tumor microenvironment," said Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies, and one of the paper’s co-authors. "Our findings reinforce that combining this novel peptide-drug conjugate with anti-PD-L1 checkpoint inhibitor therapy may yield improved clinical outcomes, with potentially profound implications for patients across various cancer types."

"An important aspect of our research is the activation of an antitumor immunity process through involvement of the cGAS/STING pathway, a key regulator in the cancer-immunity cycle," commented Prof. Borhane Annabi, Chair in Cancer Prevention and Treatment in the Chemistry Department at the Université du Québec à Montréal, and a co-author of the Frontiers in Immunology paper. "Although the animal tumor model we worked with is considered a non-immunogenetic, or ‘cold’ tumor model, we observed a net increase in leukocyte infiltration within sudocetaxel zendusortide-treated tumors, especially for tumor-infiltrating lymphocytes and tumor-associated macrophages. This realization supports the rationale for further exploration of the combination of sudocetaxel zendusortide with immunotherapy."

The article can be accessed online here.

About Immunotherapy in Cold and Hot Tumors

Immunotherapies have significantly improved the treatment of cancer. Researchers continue to explore the power of the immune system to find and destroy cancer cells. "Hot" tumors show signs of inflammation, meaning the tumor has already been infiltrated by immune cells rushing to fight the cancerous cells. Only a few types of cancers are considered to be hot. "Cold" tumors have not yet been infiltrated with T cells. This signals that the immune response is not working, making it difficult to provoke an immune response with immunotherapies. Most cancers of breast, ovary, prostate, pancreas, and brain (e.g., glioblastoma [GBM]) are cold tumors, and are largely treated with traditional therapies like radiation and chemotherapy. As a result, researchers have sought to understand how to turn cold tumors hot by reversing the suppressive microenvironment surrounding cold tumors and by attracting more of the "right" anti-tumor lymphocytes.

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting PDC, and the first compound to emerge from the Company’s broader licensed oncology platform. As a new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial in individuals with advanced ovarian cancer.

Theratechnologies has established the SORT1+ TechnologyTM platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a "scavenger" receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

On February 20, 2024 ReCode Therapeutics, a clinical-stage genetic medicines company using tissue-specific delivery to power the next wave of mRNA and gene correction therapeutics, reported that company management will participate in the upcoming February conferences (Press release, ReCode Therapeutics, FEB 20, 2024, View Source;utm_medium=rss&utm_campaign=recode-therapeutics-to-participate-in-february-conferences [SID1234640289]):

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William Blair Private Company Focus Conference
Format: Fireside Chat
Date: February 22, 2024
Time: 12:00 p.m. ET
Location: Virtual

Evercore ISI 2024 Emerging Biotech Conference
Format: Company Presentation
Date: February 28, 2024
Time: 4:00 p.m. ET
Location: Virtual

On February 20, 2024 Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene elimination, insertion, and excision, reported that it had granted Caribou Biosciences, Inc., a leading CRISPR genome-editing cell therapy company, a non-exclusive, worldwide license, with the right to sublicense, to one of Precision’s foundational cell therapy patent families for use with CRISPR in the field of human therapeutics (Press release, Precision Biosciences, FEB 20, 2024, View Source [SID1234640288]).

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The licensed patents and applications relate to Precision’s approach for targeted insertion of a sequence encoding an exogenous antigen binding receptor into the T cell receptor alpha constant (TRAC) gene locus of human T cells via a single gene edit. This approach is proprietary to Precision and results in T cells suitable for allogeneic use. The licensed family, which includes more than 20 granted U.S. and international patents, expires in October 2036.

Under the terms of the agreement, Precision will receive an upfront payment and, upon commercialization by Caribou, royalties on net sales of licensed products. In addition, for each occurrence of certain strategic transactions involving Caribou, Precision is eligible to receive a specific tiered milestone payment.

This patent family is potentially also available for non-exclusive license to other high-quality partners in the cell therapy space.

On February 20, 2024 Philogen S.p.A. (BIT:PHIL) reported that the Phase III FIBROSARC trial (NCT04650984) will continue as planned by the protocol (Press release, Philogen, FEB 20, 2024, View Source [SID1234640287]). The decision was made by an Independent Data and Safety Monitoring Board (DSMB) following the review of efficacy and safety data in the pre-planned interim analysis.

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FIBROSARC is a Phase III 1:1 randomized trial (NCT04650984) which studies L19TNF in combination with doxorubicin (Experimental Arm) versus doxorubicin alone (Control Arm) in 118 patients as first-line therapy for advanced or metastatic Soft Tissue Sarcoma (STS). The primary objective of the study is Progression Free Survival (PFS), with an estimated 45% reduction in the risk of progression in the Experimental Arm (Hazard Ratio 0.55). The pre-planned interim analysis was carried out at 50% of the expected events (i.e., one event corresponds to a disease progression or death) necessary for the primary outcome.

The 46 events required to trigger the interim analysis were reached on 9th November 2023, and at the time of this Press Release the study has enrolled 97 out of 118 patients across 24 clinical centers in Germany, Italy, France, Poland, and Spain. The enrolment of 118 patients is expected to be completed in 2024.

Prof. Dario Neri, co-founder, CEO and CSO of Philogen, commented: "We are very pleased with the recommendation of the DSMB to continue the study as planned by the protocol. The Phase III FIBROSARC trial was designed to demonstrate a significant clinical benefit of L19TNF plus doxorubicin compared to doxorubicin alone. If the final analysis is successful, the study is expected to provide an innovative treatment option for patients with advanced or metastatic STS, for whom no new paradigm-shifting therapies have been available in the last decades."

Alfredo Covelli, MD, Chief Medical Officer of Philogen, commented: "Advanced or metastatic STS are aggressive tumors still treated with chemotherapy-based regimens that were approved in the 1970s. Most innovative therapies, such as immune checkpoint inhibitors, failed to provide a significant benefit to this patient population. We are excited to record the outcome of the interim analysis of FIBROSARC and look forward to seeing the final analysis."

L19TNF is also being evaluated in (i) a Phase IIb randomized trial in first-line metastatic Leiomyosarcoma in the United States (NCT03420014), (ii) a Phase II randomized trial in pre-treated advanced or metastatic Soft Tissue Sarcoma in Europe (NCT04733183), (iii) a Phase II randomized trial in Glioblastoma at first progression in Europe (NCT04573192), and (iv) a Phase I/II/IIb trial in newly diagnosed Glioblastoma in Europe (NCT04443010). Philogen is currently launching a new Phase II study in Glioblastoma at first or later progression in the United States, based on the very encouraging preliminary data observed in the European study. These results have already been published in the journal Science Translational Medicine in 2023 (Look at al. Sci. Trans. Med. 2023, 15:eadf2281).

About Onfekafusp alfa (L19TNF, also known as Fibromun)

L19TNF is a biopharmaceutical product, proprietary to Philogen, studied for the treatment of advanced Soft Tissue Sarcoma and Glioblastoma. It consists of the L19 antibody genetically fused to Tumor Necrosis Factor (TNF). L19 binds selectively to the Extra Domain B of Fibronectin, a protein expressed in tumors (and other diseases) but absent in most healthy adult tissues. TNF is a pro-inflammatory cytokine with anti-tumor activity that is preferentially localized by the L19 antibody to neoplastic masses. L19TNF is administered via a two-hour intravenous infusion. Late-stage clinical trials with registration potential are on-going in Soft Tissue Sarcoma and Glioblastoma. The product has pan-tumoral potential and could be explored for the therapy of other cancer types (e.g., lung, breast, colon, prostate cancers).

About FIBROSARC Phase III study (NCT04650984)

FIBROSARC is a Phase III international, multi-center, randomized, comparator-controlled, parallel-group study in subjects with advanced or metastatic soft tissue sarcoma. In the study, 118 patients will be enrolled and parallel assigned in a 1:1 fashion to one of two different arms, as follows:

Experimental Arm: Patients will receive 13 μg/kg L19TNF on days 1, 3 and 5 every 3 weeks in combination with 60 mg/m2 doxorubicin (once every 3 weeks).

Control Arm: Patients will receive 75 mg/m2 doxorubicin once every 3 weeks. The sample size is calculated based on a 2-sided significance level of 5% and an 80% power, assuming a 15% rate for permanent early censoring. The statistical analysis is designed to discriminate 8 months median PFS (mPFS) in the Experimental Arm versus 4.4 months mPFS in the Control Arm. The primary analysis of PFS will occur after approximately 92 PFS events.

About advanced or metastatic Soft Tissue Sarcoma

STS is a rare group of mesenchymal cancers originating from connective tissues, which collectively account for 1% of all adult cancers. Surgery is the first line of treatment for early stage and localized disease. However, distant metastases occur in many patients, especially in those with high-grade tumors. For patients with unresectable STS, chemotherapy is the standard of treatment and doxorubicin is the recognized standard of care for first line advanced or metastatic STS.