On December 13, 2023 Engimmune Therapeutics AG ("Engimmune"), a world-class developer of soluble T-cell receptor drugs (‘TCRs’) to treat solid tumours, reported that it has entered into a collaboration with the Swiss Technology Innovation Center CSEM to accelerate the identification of safe and effective drugs using Engimmune’s unique platform (Press release, Engimmune Therapeutics, DEC 13, 2023, View Source [SID1234638545]).

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The collaboration will leverage CSEM’s high-throughput microfluidics technology to speed up the nomination of soluble TCR drug candidates with enhanced affinity, potency, and safety profiles.

Engimmune’s platform technologies – which comprise genome editing, deep sequencing, functional screening, and AI – provide a head start in the hunt for suitable soluble TCR candidates.

CSEM’s expertise in microtechnologies and droplet microfluidics will enable Engimmune to accelerate clinical candidate selection by performing safety screening at increased throughput and depth.

"Ruling out potentially harmful soluble TCRs at an early stage is vital to ensure resources are not wasted pursuing unsuitable candidates," said Felix Kurth, Group Leader Biosystems Engineering with CSEM. The collaboration is supported by a grant from Innosuisse, the Swiss Innovation Agency.

Lars Nieba, CEO of Engimmune Therapeutics, said: "We are identifying targeted, highly potent ‘off-the-shelf’ soluble TCRs, with breakthrough potential for treating solid tumour cancers. Our cutting-edge proprietary platform technologies, which combine protein engineering with AI, enable us to rapidly identify and engineer stable, soluble, multi-specific TCRs that have extremely high affinity for target cancer antigens. But finding a soluble TCR that very strongly binds to a cancer-specific tumour antigen, activates a cytotoxic response, and is also very safe can be like trying to find a needle in a haystack. Our collaboration with CSEM will help greatly to speed up that process and de-risk the development of candidates by quickly ruling out those with potential toxicities."

Dr Nieba and Engimmune’s CSO Dr Rodrigo Vazquez-Lombardi recently gave an update on the company’s approach to the in-house web publication of leading research university ETH Zürich, from which the company was spun out in 2021. The article can be found here: Redirecting immune cells against cancer | ETH Zurich.

News of the collaboration with CSEM comes ahead of Dr Nieba and Dr Vazquez-Lombardi presenting Engimmune’s technologies and immuno-oncology assets at the Biotech Showcase in San Francisco on January 8.

On December 13, 2023 Halia Therapeutics, a clinical-stage biopharmaceutical company pioneering a novel class of small molecule medications designed to combat inflammation, reported the dosing of the first patient in Phase 2a clinical trial evaluating its lead candidate, HT-6184, for the treatment of lower-risk myelodysplastic syndromes (LR-MDS) (Press release, Halia Therapeutics, DEC 13, 2023, View Source [SID1234638544]). HT-6184 is a selective and orally bioavailable first-in-class inhibitor of NLRP3/NEK7 inflammasome, a main driver of inflammatory diseases, as well as hematologic and other malignancies.

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Myelodysplastic syndromes are a group of cancers in which the bone marrow produces underdeveloped (immature) cells that are abnormal in size, shape, or appearance, which are called "dysplastic. This leads to a reduced number of healthy blood cells, which can result in multiple complications, including but not limited to anemia, recurrent infections, and progression to cancer. The trial will evaluate the safety and activity of HT-6184 in up to 40 patients with LR-MDS and will be conducted at multiple sites across India. The study will measure the rate of hematological improvement, including transfusion dependency and changes in hemoglobin levels as primary endpoints for the study. Secondary endpoints will further assess the effect of HT-6184 on biomarkers of inflammasome activation in MDS and the changes in clone size of somatic gene mutations. The trial is expected to be completed by Q4 2025.

"The dosing of the first patient in our Phase 2 trial of HT-6184 marks a significant milestone for Halia in further evaluating the potential of targeting the NLRP3 inflammasome to treat a wide spectrum of immunological and inflammatory diseases," said Margit M. Janát-Amsbury, MD, Ph.D., Chief Medical Officer of Halia Therapeutics. "The recent positive results of our Phase I trial investigating HT-6184 are extremely encouraging and highlight the functional activity of HT-6184 in being able to reduce inflammatory cytokines. As we move into this next stage of clinical testing, we look forward to assessing the potential benefit of our inflammasome inhibitor for MDS patients, as well as for other patients who suffer from inflammation-related diseases."

Halia recently announced Phase I trial results evaluating HT-6184, which was shown to be safe, well tolerated and to significantly reduce NLRP3-inflammatory cytokines in healthy volunteers.

About NLRP3
NLRP3, an innate immune sensor, is activated in response to various pathogenic and sterile stimuli. Activation of NLRP3 triggers the release of the pro-inflammatory cytokines IL-1β and IL-18 and induces a lytic cell death process called pyroptosis. These processes lead to systemic chronic inflammation. Halia’s therapeutic inhibition of NLRP3 prevents the formation of the NLRP3 inflammasome and promotes its disassembly once formed, thereby inhibiting the production and release of IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome is thought to drive the onset and progression of many conditions, including fibrotic, dermatological, and auto-inflammatory diseases. Significant neurodegenerative and neuroinflammatory disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are also driven by NLRP3 activation. Notably, in recent years, NLRP3 has been discovered and is gaining significance as one of the key biological drivers of ineffective hematopoiesis and inflammation in MDS.

About HT-6184
HT-6184 represents an innovative approach as it is the first drug candidate to target the protein NEK7 through an allosteric mechanism. NEK7 is an essential component of the NLRP3 inflammasome and is critical for its assembly and the maintenance of NLRP3 activity. In preclinical models, Halia has shown that inhibiting the ability of NEK7 to bind to NLRP3 leads to a disruption in the formation of the NLRP3 inflammasome complex, thereby inhibiting the signaling from the inflammasome and reducing the inflammatory response. Preclinical models also showed that in addition to disrupting the formation of the NLRP3 inflammasome, HT-6184 promotes the disassembly of the inflammasome once activated.

On December 13, 2023 ChemDiv Inc., dedicated to partnering in discovery and development of breakthrough therapies based on its unique chem-bio platforms, reported the presentation of non-clinical summary data for the best-in-class selective BCL2 inhibitor clinical candidate at the 65th ASH (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA (Press release, ChemDiv, DEC 13, 2023, View Source [SID1234638543]).

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"A Novel Selective BCL2 Inhibitor with Limited Immune Suppression and Improved Safety Compared to Venetoclax" was presented by collaborators from University of Cincinnati (Ohio), Molsoft LLC, Expert Systems Inc of San Diego California, and Eilean Therapeutics LLC of Dover, Delaware. The presentation highlighted best-in-class potency and selectivity against BCL2, a key pro-survival protein that is overexpressed in many cancers. This clinical candidate demonstrated an equivalent in vivo anti-tumor efficacy as venetoclax in both B cell and myeloid malignancy cell lines and in vivo models. Compared to venetoclax, the candidate exhibits significantly less suppression of non-malignant immune cell populations, a result that signals superior selectivity and improved safety profile.

In collaboration with rational design groups of Molsoft and Expert Systems, John Byrd’s lab at University of Cincinnati, ChemDiv deployed a fragment-based approach to completely redesign a binding interface comparing to venetoclax and venetoclax-like molecules to achieve differentiated pharmacology according to the target product profile. The 4600-fold selectivity for BCL2 over BCL-xl; high oral bioavailability, short half-life and low interaction with CYP3A of the resulting clinical candidate translated in best-in-class safety, tolerability and developable pharmacology advantages delivered to partners at Eilean Therapeutics LLC.

On December 13, 2023 Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting photoimmunotherapy treatments based on its proprietary Alluminox platform, reported that the Company will present at the 42nd Annual J.P. Morgan Healthcare Conference being held January 8-11, 2024 (Press release, Rakuten Medical, DEC 13, 2023, View Source [SID1234638542]).

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Rakuten Medical’s Co-Chief Executive Officer and President, Takashi Toraishi, and Chief Operating Officer, Abhijit Bhatia, are scheduled to present on Wednesday, January 10 at 2:30 pm PST. They will also participate in one-on-one investor and partnering meetings during the conference.

A live webcast of the presentation can be accessed by the following link. A replay of the webcast will also be archived at the same location.
Link to the webcast of Rakuten Medical’s presentation at J.P. Morgan Healthcare Conference 2024

Investors and analysts who would like to schedule a one-on-one meeting with Rakuten Medical Leadership at the conference venue can request a meeting at 1on1 meeting request form.

Following the completion of the presentation, a full recording and presentation slides will be available in the Events & Presentations section of the Rakuten Medical website.

On December 13, 2023 Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics") reported that its CSF-1R inhibitor pimicotinib (ABSK021) has been granted the fast track designation ("FTD") by the U.S. FDA for the treatment of tenosynovial giant cell tumor ("TGCT") patients that are not amenable to surgery (Press release, Abbisko Therapeutics, DEC 13, 2023, View Source [SID1234638541]). Previously, pimicotinib was granted the breakthrough therapy designation ("BTD") by the U.S. FDA for TGCT in January, 2023. The grant of FTD and BTD will accelerate the global development and commercialization of pimicotinib.

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Fast Track is a policy designed to facilitate the development and expedite the review of drugs in order to treat serious conditions and fulfill unmet medical needs. Its purpose is to get important new drugs to patients earlier. Moreover, the FTD enables companies to maintain more frequent communications and meetings with the U.S. FDA. The drug also becomes eligible for accelerated approval and priority review by the U.S. FDA.

In early December, Abbisko entered into an agreement with Merck KGaA, Darmstadt, Germany that grants it the exclusive license to commercialize pimicotinib for all indications in China mainland, Hong Kong, Macau, and Taiwan. Merck KGaA, Darmstadt, Germany also obtained an exclusive option for global commercial rights of pimicotinib, subject to the terms and conditions as agreed between the parties. Pursuant to the terms of the License Agreement, Abbisko will receive a one-time, non-refundable down payment of US$ 70 million. In the event that Merck KGaA, Darmstadt, Germany exercises the global commercialization option, Merck KGaA, Darmstadt, Germany will pay Abbisko an additional option exercising fee. The aggregate amounts of upfront payment, option exercising payment, and payment for development and commercialization milestones will total US$ 605.5 million. Abbisko will also obtain from Merck KGaA, Darmstadt, Germany double-digit percentage (%) royalties based on actual annual net sales.

Pimicotinib is a novel, orally available, highly selective, and potent small molecule CSF-1R inhibitor, independently developed by Abbisko Therapeutics. It has been granted the BTD and Priority Medicine (PRIME) designation by China NMPA, U.S. FDA, and EMA for the treatment of TGCT patients that are not amenable to surgery. The study is the first global Phase III clinical trial of TGCT conducted simultaneously in China, the U.S., Canada and Europe.

Upon 1-year follow-up in a Phase 1b trial for TGCT, pimicotinib demonstrated an ORR of 87.5% (28/32, including 3 CR) in the 50 mg QD cohort, which was presented at the 2023 CTOS. A Phase I dose-escalation trial for pimicotinib has been completed in the U.S. previously.

In addition to TGCT, Abbisko is actively exploring the potential of pimicotinib in treating other indications including many types of solid tumors in clinic, and it has obtained approval from NMPA to conduct a Phase II clinical study in chronic graft-versus-host disease and advanced pancreatic cancer. Up until today, no highly selective CSF-1R inhibitors have been approved in China.

About TGCT

TGCT is a locally aggressive neoplasm that usually affects synovial joints, mucous sacs, and tendon membranes, resulting in swelling, pain, stiffness, and decreased activity of the affected joints, which seriously affects the patient’s quality of life [1]. According to the 2013 World Health Organization classification, TGCTs were classified as localized TGCT and diffuse TGCT. Diffuse TGCT encompasses formerly known nodular tenosynovitis and pigmented villonodular synovitis ("PVNS"). Overexpression of CSF-1 occurs in most TGCTs. Surgical resection is the standard treatment for TGCT. However, not all patients are suitable for surgical treatment. It is difficult to remove tumors of diffuse TGCT patients by surgery, which may possibly lead to severe joint damage, total synovectomy, joint replacement, or even amputation, and the risk of surgical complications can be high. It has been reported that more than 50% of patients with diffuse TGCT would undergo recurrence after surgical resection [2]. For TGCT patients who are not amenable to surgery, there is currently no approved drug available in China.