On December 18, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported the expansion of its pipeline with a novel FAP-targeted radiopharmaceutical for the diagnosis and treatment of cancer (Press release, Clarity Pharmaceuticals, DEC 18, 2024, View Source [SID1234649191]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

FAP is expressed on cancer associated fibroblasts (CAFs), a particular cell type found in the tumour microenvironment (cancer ‘infrastructure’ called the tumour stroma). CAFs are found in a broad range of cancers (e.g. breast, colorectal, pancreatic, lung, brain and ovarian cancers), but only minimally in normal tissue, making FAP a promising pan-cancer target for both imaging and treatment of cancers1. CAFs form part of the environment surrounding the cancer cells, and they can promote cancer growth and the spread of the tumour throughout the body2. Targeting the tumour stroma is an alternative way to treat cancer whereby the architecture of the tumour mass is targeted rather than the tumour cells directly.

Clarity’s Targeted Copper Theranostic (TCT) targeting FAP was developed at the benchtop of Australian science, with a clear understanding of other FAP-targeted radiopharmaceuticals in development and the intent of overcoming the low uptake and retention of these agents in tumours. This was achieved by utilising some novel chemistry, and by combining an industry leading FAP inhibitor with the proprietary SAR chelator technology. The SAR Technology enables the use of copper-64 (64Cu) for imaging and copper-67 (67Cu) for the targeted treatment of various cancers.

Similar to how Clarity developed its PSMA-targeted prostate cancer agent as a dimer, SAR-bisPSMA, which was designed to improve tumour uptake and retention, the Company created a novel dimer for its FAP-targeted radiopharmaceutical, SAR-bisFAP. With the benefit of comparing this novel molecule to other FAP radiopharmaceuticals in development as well as to a monomer equivalent (SAR-monoFAP), the dimer SAR-bisFAP has shown increased tumour uptake and retention over 24 hours in pre-clinical models.In addition to comparing the mono and dimer versions of the product, Clarity compared the dimer, 64Cu-SAR-bisFAP, to an industry standard FAP-targeted monomer called 68Ga-FAPI-46. Using a FAP-expressing melanoma cell line (SK-MEL187) in this experiment, at 1-hour post-injection 64Cu-SAR-bisFAP had approximately 4 times the uptake in the cancer compared to 68Ga-FAPI-46. The improvements in uptake and retention of 64/67Cu-SAR-bisFAP compared to first-generation FAP compounds, such as FAPI-46, are key attributes for the development of next-generation radiopharmaceuticals.

Clarity is currently conducting additional investigations to enable a Phase I clinical trial, which could commence in late 2025. Research into the potential clinical use of Clarity’s FAP agent has begun with several pre-clinical studies in diagnostics (utilising 64Cu-SAR-bisFAP), which will be followed by exploring treatment opportunities of cancers based on their unmet medical needs (using 67Cu-SAR-bisFAP).

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "Our commitment to always putting science first at Clarity has placed us in an enviable position in radiopharmaceuticals globally. This has allowed us, yet again, to create a novel product at the benchtop to overcome the shortcomings of competing radiopharmaceuticals by increasing the uptake and retention of the molecule over time. Coupled with the use of the perfect pairing of copper isotopes, this facilitates the use of same-day and next-day imaging, addressing the issue of low sensitivity of short half-life products using gallium-68 and fluorine-18, as well as potentially enhancing the therapeutic benefit through increasing the amount and retention of the product at the site of tumours. This is especially the case for FAP-targeted radiopharmaceuticals that offer so much hope as a pan-cancer but suffer the issue of low uptake and retention at the tumour site.

"We are excited to continue growing our pipeline of TCTs through our Discovery Program, utilising the unique advantages of copper isotopes, enabled by our proprietary SAR Technology. Unlike other chelator technologies that leak copper in vivo, the SAR Technology securely holds copper over time, unlocking a myriad of advantages of the "perfect pairing" of copper-64 for imaging and copper-67 for therapy, such as next-day imaging, supply, logistical and environmental advantages. Having strong intellectual property around the SAR Technology, as well as our novel products, with over 28 patent families now within the Company, we continue expanding our pipeline of next-generation radiopharmaceuticals. The development of these new products is only possible due to the utilisation of great chemistry combined with new promising targets and our proprietary chelator, thereby enabling a multitude of new products for indications with high unmet needs. By going back to the drawing board and conducting comprehensive research and testing, we were able to create a unique product that achieves the outcomes we were looking for of improving uptake and retention in tumours. The tumour targeting, retention and pharmacokinetic data we have seen to date with SAR-bisFAP is impressive, and we look forward to progressing this product in clinical trials and are excited to explore the pan-cancer targeting potential in a range of indications with high unmet needs."

About 64/67Cu-SAR-monoFAP and 64/67Cu-SAR-bisFAP
64/67Cu-SAR-monoFAP and 64/67Cu-SAR-bisFAP are unregistered products. Their safety and efficacy have not been assessed by health authorities such as the US Food and Drug Administration (FDA) or the Therapeutic Goods Administration (TGA). Outcomes from human clinical trials may differ from pre-clinical findings. There is no guarantee that these products will become commercially available.

On December 17, 2024 HighField Biopharmaceuticals, a clinical stage company using lipid-based therapeutics to treat cancer, diabetes and other diseases, reported that the Center for Drug Evaluation of China’s National Medical Products Administration has granted clearance of the company’s Investigational New Drug (IND) application to begin a clinical trial of HF50 in patients with advanced solid tumor cancers (Press release, HighField Biopharmaceuticals, DEC 17, 2024, View Source [SID1234649187]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This is a highly significant milestone for our company and for patients," said Yuhong Xu, Ph.D., CEO and Scientific Founder of HighField. "HF50 is a T cell Redirecting Antibody Fragment-anchored Liposome, or TRAFsome, with two different antibodies attached; the first binds to T cells and the second binds to tumor cells. It is the first-of-its-kind liposomal T cell engager to emerge from our platform of immunoliposomes, and the first to enter clinical trials."

In addition to converting T cells into an army of cancer destroyers, HF50 also carries a payload that releases in the tumor microenvironment to facilitate the anti-tumor immune reactions.

The design of the TRAFsome T cell engagers builds upon the success of HighField’s LipoADCplexTM platform. The first product from this platform is K1, which contains the anti-HER2 antibody for binding to tumor cells and delivering cancer killing drugs. K1 is in clinical trials and has shown very good safety profiles in cancer patients.

"Once we proved the LipoADCplexTM platform could be safer, cheaper and more effective than ADCs (antibody-drug conjugates), the next logical step is to enlist immune cells with a second antibody to enable immunotherapy against the target cells," Dr. Xu explained. "T cell engagers can be very powerful. But over stimulation may result in high risk of toxicity and T cell exhaustion."

The Phase 1 open-label, dose escalation and dose expansion trial of HF50 will evaluate the safety, tolerability, pharmacokinetic characteristics, immunogenicity, and preliminary efficacy in patients with advanced solid tumors. The trial is expect to begin in 1Q2025.

"As a T cell engager, HF50 has advantages over bispecific antibody constructs and even CAR T cells," Dr. Xu said. "The liposomal T cell engagers can integrate three specific activities. The first is to activate T cells; the second is to direct the T cells to target cells; and the third is to release the payload to facilitate the immune responses."

Dr. Xu added, "The TRAFsomes can be made modularly with low costs. Preclinical data suggested they are much safer and more effective. We can also add different payloads to expand their application to other illnesses such as autoimmune diseases and illnesses related to aging."

On December 17, 2024 Akamis Bio, a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene (T-SIGn) therapy platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors, reported $60 million in funding linked to the close of a Series A Prime financing round and entry into a strategic partnership for the development of its lead clinical candidate, NG-350A (Press release, Akamis Bio, DEC 17, 2024, View Source [SID1234649185]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The new funding will support the company’s work to advance NG-350A through a Phase 1b clinical proof-of-concept (PoC) study in patients with locally advanced rectal cancer (LARC). NG-350A is an intravenously delivered, transgene-armed tumor gene therapy designed to drive intratumoral expression of a CD40 agonist monoclonal antibody in both primary and metastatic epithelial-derived solid tumors. The Phase 1b PoC study, known as FORTRESS (NCT06459869), will evaluate clinical complete response (cCR) rates to NG-350A in combination with chemoradiotherapy (CRT) in adult patients with LARC and at least one risk factor for local or distant recurrence.

The Series A Prime financing was led by Sedgwick Yard, a global biotech venture capital firm with Greater China roots. In a separate transaction, Akamis Bio entered into a licensing agreement granting Xuanzhu Biopharma the Greater China Region Rights to NG-350A. Under the terms of the licensing agreement, Akamis Bio is eligible to receive undisclosed upfront payments plus regulatory and sales milestones, as well as tiered royalties in the high single- to low double-digit range on Greater China Region NG-350A sales.

"We are grateful for this strong vote of confidence in NG-350A, the T-SIGn platform and the Akamis Bio team. The Sedgwick Yard-led Series A Prime financing and Xuanzhu Biopharma licensing deal demonstrates our shared commitment with these partners to rapidly advancing NG-350A while also demonstrating the broader potential of T-SIGn," said Howard Davis, PhD, CEO of Akamis Bio. "Compelling clinical data from our prior studies have shown the consistent safety profile of T-SIGn, as well as the potential of intravenously-delivered NG-350A to drive sustained transgene expression capable of altering the tumor microenvironment. Our aim over the next 12-18 months is to deliver clinical proof-of-concept data for NG-350A via the FORTRESS study."

"We believe T-SIGn offers a true platform approach and that NG-350A is just the beginning of what we anticipate will become a robust pipeline of IV-delivered, tumor-targeted immunotherapies. We are very confident in the scientific and drug development acumen of the Akamis Bio management team, as well as in their ability to deliver on this opportunity to advance the standard of care for patients with difficult to treat solid tumors," said Richard Shen, Managing Director, Sedgwick Yard.

A recently published paper in the Journal for ImmunoTherapy of Cancer (JITC), described data from the FORTITUDE first-in-human dose escalation study in patients with metastatic/advanced epithelial tumors that provided initial proof-of-mechanism for NG-350A and highlighted the advantages of its intravenous route of administration. These data demonstrated the consistent safety profile of NG-350A, as well as providing strong evidence of tumor-selective delivery, replication and transgene expression. Additionally, this study demonstrated that intravenous delivery of NG-350A results in a superior overall pharmacokinetic and pharmacodynamic profile, with no apparent disadvantages versus intratumoral injection.

"We are thrilled to partner with Akamis Bio to develop and commercialize NG-350A in the Greater China Region. The T-SIGn platform has the potential to revolutionize the treatment of advanced metastatic solid tumors, and we look forward to working closely with the Akamis Bio team to bring this novel tumor gene therapy to patients," said Jiakui Li, PhD, CEO of Xuanzhu Biopharma.

Linked to the close of the Series A Prime financing, Akamis Bio added two new members to its Board of Directors: Richard Shen, Managing Director, Sedgwick Yard, and Adrian Chan, Managing Director, Sedgwick Yard.

About T-SIGn

Akamis Bio’s T-SIGn therapeutics are based on a replication competent, chimeric group B adenovirus backbone which has been adapted via directed evolution to home specifically to both primary and metastatic epithelial-derived solid tumor tissue following intravenous delivery. Once at the tumor site, T-SIGn therapeutics can drive the intratumoral expression of multiple transgene payloads, turning solid tumor cells into "drug factories" while leaving healthy tissue unaltered and intact. The intratumoral expression of immunologically active biomolecules and therapeutic proteins can result in the remodeling of the solid tumor microenvironment, triggering robust antitumor immune responses. T-SIGn therapeutics have the potential to be used in the monotherapy setting, as well as in combination with other immuno-oncology agents to target the key mechanisms that tumors use to evade the immune system.

On December 17, 2024 Indapta Therapeutics, Inc., a privately held clinical stage biotechnology company developing next-generation cell therapies for the treatment of cancer and autoimmune diseases, reported it has closed a $22.5 million round of new financing to accelerate the clinical development of its differentiated allogeneic Natural Killer (NK) cell therapy (Press release, Indapta Therapeutics, DEC 17, 2024, View Source [SID1234649183]). Current investors RA Capital Management, LP, Leaps by Bayer, the impact investment arm of Bayer AG, Vertex Ventures HC, Pontifax, and the Myeloma Investment Fund, the venture philanthropy subsidiary of the Multiple Myeloma Research Foundation, completed the round.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This funding will enable us to generate significant additional data in our ongoing trial of IDP-023 in cancer as well as initial data from our first trial in autoimmune disease," said Mark Frohlich, Indapta’s CEO. "Preliminary results of IDP-023 in cancer are encouraging and we look forward to initiating our Phase 1 trial for multiple sclerosis in Q1 2025. This financing, together with our recently announced collaboration with Sanofi, highlights the promise of our differentiated platform."

Advancing Clinical Trials of Lead Product IDP-023

Indapta has completed enrollment in the safety run-in portion of the Phase 1 clinical trial of IDP-023 in Non-Hodgkin’s Lymphoma (NHL) and Multiple Myeloma (MM), in which patients received up to three doses of IDP-023 without and with interleukin (IL)-2. As presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting, the mean maximum decrease in serum M-protein or light chain was 73% in responding myeloma patients with relapsed/refractory disease, with three patients achieving a reduction of 84% or greater. Enrollment of cohorts receiving IDP-023 in combination with monoclonal antibodies targeting CD20 or CD38 is underway.

In August, Indapta announced FDA clearance of its IND of IDP-023 in combination with ocrelizumab in progressive MS. The company’s approach is highly differentiated from other cellular approaches to autoimmune diseases, with at least three different mechanisms that can address the biology of the disease: 1) by combining with a B cell targeting antibody like ocrelizumab, IDP-023 can deplete B cells more effectively than antibody alone; 2) g-NK cells are capable of targeting autoreactive T and B cells that are known to upregulate HLA-E; and 3) given their inherent anti-viral activity, g-NK cells can potentially address the EBV viral reservoir that contributes to the disease pathogenesis.

On December 17, 2024 TAE Life Sciences (TLS), a leading developer of Boron Neutron Capture Therapy (BNCT) systems and drugs, and the Italian National Center for Oncological Hadrontherapy (CNAO), a premier hadrontherapy center in Europe, reported a definitive agreement to collaborate on groundbreaking global drug research and development initiatives for the implementation of BNCT (Press release, TAE Life Sciences, DEC 17, 2024, View Source [SID1234649182]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This strategic partnership will bring together the expertise of two innovative leaders in cancer treatment, with the purpose to revolutionize cancer care through BNCT, a targeted radiation therapy designed to improve outcomes for patients with complex and metastatic cancers. CNAO’s extensive experience in hadrontherapy, encompassing proton, carbon ions and other particles, complements TLS’s leadership in advancing cancer treatment with BNCT technology and drug development.

BNCT is a type of combination cancer treatment that uses neutron radiation and a special boron compound to target and destroy cancer cells. The process involves two main steps. In the first one, a boron-rich compound is administered to the patient, typically via injection or infusion. This compound is designed to be selectively absorbed by cancer cells, with minimal uptake by normal tissues. In the second step, after the boron compound has been absorbed by the cancer cells, the patient is exposed to a beam of low-energy neutrons. These neutrons interact with the boron atoms within the cancer cells and destroy them.

In late 2020, CNAO had already entered into an agreement with TLS to adopt the BNCT system and install an accelerator-based neutron source in Italy. Now, the new agreement completes the collaboration, including the drug development as well.

Prof. Gianluca Vago, CNAO President, commented: "Our mission has always been to leverage cutting-edge technologies to expand treatment opportunities for the benefit of cancer patients. Being chosen by TLS for such an important collaboration is a further recognition of CNAO’s expertise in particle therapies, both in clinical and research activities. For this project, our center will work in close cooperation with University of Pavia, Polytechnic University of Milan, National Institute for Nuclear Physics and Fondazione IRCCS Policlinico San Matteo of Pavia. The partnership with TLS will enable us to open up new frontiers in BNCT and make CNAO a unique facility in the world to combine treatments with protons, heavy ions (carbon ions and other species) and neutrons."

Planned Milestones and Key Objectives:

Installation and Clinical Trials: The installation of TLS’s Alphabeam BNCT system at CNAO is scheduled to begin in 2025, with clinical trials launching in 2026. The initial trials will leverage Steboronine (Boronophenylalanine, BPA)—an boron drug developed by Stella Pharma for BNCT and distributed by TLS in Europe and the US. Steboronine selectively accumulates boron in cancer cells and is already approved in Japan for recurrent head and neck cancers, the focus of these first trials.
Advancing Cancer Treatment: The collaboration is poised to expand the clinical applications of BNCT to address a wide range of cancers, including metastatic cancers, offering new hope for patients worldwide.
CNAO NEXT Services: The partnership includes efforts to promote the range of services offered by CNAO NEXT, an independent company set up by CNAO, which operates in the field of precision therapies, providing technical and clinical consultancy and assisting other centers in implementing particle therapies.
A significant aspect of the collaboration involves the clinical implementation and commercialization of new TLS BNCT drugs, such as Boronotyrosine (BTS), which has shown promising preclinical results in animal models. "Our partnership with CNAO marks a transformative step in advancing BNCT as a next-generation cancer therapy," said Rob Hill, CEO of TAE Life Sciences. "Together, we aim to push the boundaries of cancer treatment and provide groundbreaking solutions to patients who need them most."

Additionally, prof. Lisa Licitra, Scientific Director of CNAO, Chief of Head and Neck Cancer Medical Oncology Dept at Fondazione IRCCS Istituto Nazionale dei Tumori, Associate Professor at the University of Milan, has joined the TLS Clinical Advisory Board as an internationally recognized leader in head and neck oncology. She will serve as leading oncologist for the BNCT clinical trials at CNAO focusing on head and neck cancer and will oversee the clinical trial at CNAO, further strengthening the collaboration’s scientific foundation.

Prof. Lisa Licitra, Scientific Director of CNAO, affirmed: "BNCT has demonstrated compelling responses for recurrent or refractory tumours, such as head and neck cancers. Therefore, working with Prof. Ester Orlandi, Head of CNAO Clinical Department, we will initially focus on patients with this type of tumours. With the introduction of BNCT, we can reduce treatment to 1-2 sessions, expand therapeutic indications and potentially offer new hope to patients with metastatic tumours. Our goal will be to offer increasingly customized therapeutic options, by having at our disposal a wide range of particles: not only protons and carbon ions but also neutrons for BNCT, helium and oxygen."