On May 23, 2024 Amphista Therapeutics ("Amphista"), a leader in next generation targeted protein degradation (TPD) approaches, reported the unveiling of a new mechanism of action for the degradation of BRD9, an emerging target in oncology, that is differentiated from cereblon- or VHL-based PROTACs, during an oral presentation at the 2024 Protein Degradation in Focus Symposium held in Dundee, UK (Press release, Amphista Therapeutics, MAY 23, 2024, View Source [SID1234643575]).

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This significant news for the TPD field builds upon an earlier announcement by Amphista of two compelling data sets demonstrating in vivo efficacy and central nervous system (CNS) activity of its mechanistically differentiated protein degraders. At today’s presentation titled "Degradation of BRD9 by a novel targeted glue", Dr Andrea Testa, Scientific Co-Founder and Senior Director, Discovery Chemistry showed data from proteomic and genetic validation studies which demonstrate that Amphista’s bifunctional degraders induced degradation of BRD9 by target-assisted E3 ligase recruitment. This novel mechanism selectively induces the proximity of BRD9 to DCAF16 and serves as a molecular glue. DCAF16 is a cullin-RING E3 ligase which can facilitate degradation of proteins of interest via ternary complex formation. Induction of this complex leads to deep and rapid degradation of BRD9 in vivo.

Louise Modis, Chief Scientific Officer of Amphista Therapeutics, said: "The discovery of a novel mechanism for BRD9 degradation, differentiated from cereblon- or VHL-based PROTACs, is a testament to Amphista’s proprietary chemistry and know-how. Our ability to translate this novel approach into high-quality, drug-like compounds with oral bioavailability and activity in vivo is truly exciting. As we continue to spearhead our efforts to advance new TPD approaches, our goal remains clear – to expand the offering of TPD medicines beyond CRBN and VHL-based agents and bring effective treatments to patients in areas of high unmet need."

In the results presented, Amphista’s sub-nanomolar BRD9 degraders showed activity in both solid and liquid cancer cell lines and demonstrated a high degree of selectivity over 8,000 proteins quantified by proteomics, including the closely related proteins BRD7 and BRD4. Notably, these compounds induced BRD9 degradation in a mouse xenograft model illustrating Amphista’s BRD9 degraders are orally bioavailable and active in vivo. This is the first-time in vivo degradation of BRD9 has been demonstrated via DCAF16, underscoring the potential therapeutic application of Amphista’s bifunctional degraders.

Building on this knowledge, Amphista is applying its proprietary scientific know-how and expertise to the development of targeted glues which induce degradation of different targets, expanding the opportunity beyond BRD9. Future announcements will provide details of additional pipeline targets as part of Amphista’s ambitions to develop a first- and/or best-in-class portfolio of degraders with leading physicochemical properties.

On May 23, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported it will participate in the TD Cowen 5th Annual Oncology Innovation Summit (Press release, Allogene, MAY 23, 2024, View Source [SID1234643571]).

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TD Cowen 5th Annual Oncology Innovation Summit
Tuesday, May 28, 2024
9:30am PT/12:30pm ET

The webcast will be posted to the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following a live webcast, a replay will be available on the Company’s website for approximately 30 days.

On May 23, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that two clinical abstracts on its lead drug candidate mitazalimab, a best-in-class CD40 agonist, in first line metastatic pancreatic cancer will be presented (abstracts 2569 and 4133) in a poster presentation session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place in Chicago, IL and online during May 31-June 4 (Press release, Alligator Bioscience, MAY 23, 2024, View Source [SID1234643569]).

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Data presented at ASCO (Free ASCO Whitepaper) from the OPTIMIZE-1 study, of mitazalimab in combination with mFOLFIRINOX chemotherapy, showed that pharmacological analyses identified mitazalimab-induced expansion of CD4 effector T cells one week after first administration as a correlate of treatment outcomes. These data suggest the contribution of mitazalimab to tumor responses, and further supports the unique trial design of OPTIMIZE-1.

OPTIMIZE-1 achieved its primary endpoint, demonstrating a confirmed Objective Response Rate (ORR) of 40.4%, an unconfirmed ORR of 50.9% and a disease control rate (DCR) of 79% in 57 evaluable patients, as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). This compares favorably to the ORR of 31.6% reported in a similar patient population treated with FOLFIRINOX alone.[1] Median Duration of Response (DoR) was 12.5 months, remarkably longer than reported so far with any other approved and investigational therapies. Median Overall Survival (OS) was 14.3 months and the survival estimate from the next planned analysis may further improve.

"Most pancreatic cancer patients are diagnosed after the disease has already metastasized. Treatment options at this stage are rather unsatisfactory and there is a major need of novel therapies for these patients. The primary analysis results of OPTIMIZE-1 study suggest that adding mitazalimab to the modified FOLFIRINOX regimen significantly prolongs the durability of response, resulting in a meaningful extension of overall survival in this fatal disease. It is indeed encouraging to see many patients still continuing in the study, and we are very much looking forward to the 18-month survival follow-up from OPTIMIZE-1, which we expect at the end of June 2024," said Dr. Sumeet Ambarkhane, CMO of Alligator Bioscience. "These results support the continued development of mitazalimab in combination with mFOLFIRINOX, in a confirmatory, phase 3, clinical trial in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). Furthermore, the correlation of mitazalimab-induced immune activation with improved clinical outcomes suggests a potential immunological profile that could be used as a biomarker for this treatment."
The open-label, multi-center OPTIMIZE-1 study assessed the safety and efficacy of mitazalimab (CD40 mAb agonist) in combination with standard of care chemotherapy mFOLFIRINOX, in previously untreated, chemotherapy naïve patients. More details can be found with the clinicaltrials.gov identifier NCT04888312.

Poster Presentations Details
Title: CD4 effector T cell expansion to identify objective responses to the CD40 agonist mitazalimab in combination with modified FOLFIRINOX (mFFX) as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC) in the OPTIMIZE-1 study
Presenter: Peter Ellmark, PhD
Abstract: 2569
Track: Developmental Therapeutics—Immunotherapy
Location: Hall A | On Demand
Time: 1 June 2024, 09:00 – 12:00 (GMT-5)

Title: OPTIMIZE-1 primary analysis: Safety, efficacy and biomarker results of a phase 1b/2 study combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC)
Presenter: Jean-Luc Van Laethem, MD, PhD
Abstract: 4133
Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
Location: Hall A | On Demand
Time: 1 June 2024, 13:30 – 16:30 (GMT-5)

[1] Conroy et al., N Engl J Med 2011; 364:1817-1825; DOI: 10.1056/NEJMoa1011923

About pancreatic cancer

Pancreatic cancer is the 12th largest cancer by number of patients. It is expected to become the second leading cause of cancer death in the western world by 2030. There are about 200,000 annual cases in the U.S. and the EU, with very poor prognosis: five-year survival is about 10% and median survival about 6 months. For 80% of patients, the only option is chemotherapy that offers only marginal benefit. FOLFIRINOX is expected to be the preferred first line regimen in the U.S. and the EU for patients with good performance status.

On May 23, 2024 2seventy bio, Inc. (Nasdaq: TSVT) reported that members of the management team will present at the following upcoming investor conferences (Press release, 2seventy bio, MAY 23, 2024, View Source [SID1234643567]):

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TD Cowen 5th Annual Oncology Innovation Summit: Insights for ASCO (Free ASCO Whitepaper) & EHA (Free EHA Whitepaper) in a virtual fireside chat on Tuesday, May 28, 2024 at 8:30 a.m. ET
Goldman Sachs 45th Annual Global Healthcare Conference in Miami Beach, FL, on Monday, June 10, 2024 at 8:40 a.m. ET

Live webcasts of the fireside chats will be available via the Investors and Media section of the company’s website at View Source Replays will be archived on the 2seventy bio website for 30 days following the events.

On May 22, 2024 Captain T Cell GmbH, a biotechnology company developing next-generation T cells against solid tumors, reported the successful closing of a seed financing round totaling € 8.5 million (Press release, Captain T Cell, MAY 22, 2024, View Source [SID1234644416]). A syndicate of experienced life science investors including i&i Biotech Fund I SCSp, Brandenburg Kapital GmbH, and HIL-INVENT Ges.m.b.H participated in the round. In addition, the German Federal Ministry of Education and Research (BMBF) is supporting the Company through its prestigious GO-Bio program. The financing also marks the appointment of biotech veteran Jörn Aldag as Chairman of the Board of Directors.

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The funds will be used to further progress Captain T Cell’s first-in-class lead program towards the clinic along with a novel allogeneic platform for off-the-shelf treatments of solid tumors.

Captain T Cell develops first-in-class efficacy-enhanced TCR-T cells for solid tumors that are not addressed by existing therapies. Using a toolbox of next-generation technologies, Captain T Cell generates TCR-T cells with enhanced persistence and the capacity to cope with the hostile tumor microenvironment of difficult-to-treat solid tumors. In preclinical in vivo models, the Company has been able to completely eradicate aggressive tumors using these efficacy-enhanced T cells. A key technology established by the Captain T Cell team is its proprietary TCR-ALLO platform for off-the-shelf treatment of solid tumors. The TCR-ALLO platform is a versatile tool that can be expanded to a variety of cancer indications.

The Company is a spin-off from the renowned Max Delbrück Center, Berlin, Germany, a leading European biomedical research institution. The institute provided valuable financial and infrastructural support throughout the pre-seed phase and together with its technology transfer partner Ascenion remains a close partner for future endeavors.

Dr. Felix Lorenz, CEO of Captain T Cell, said: "This successful financing round allows us to accelerate our high-potential therapies and brings us closer to providing life-saving options for patients underserved by current treatments. We are steadfast in our mission to progress our lead candidate towards the clinic and to establish our TCR-ALLO platform as a leader in off-the-shelf solid tumor therapeutics."

"We have been following the Captain T Cell team for some time and have been impressed by their scientific depth and management capabilities. The team has generated highly convincing preclinical data. Also, we see tremendous potential in their off-the-shelf approach. It holds the promise of bringing life-saving therapies to patients at much lower cost. If successful, it could be applied to any TCR-T cell therapy currently in development, enabling widespread use of these therapies. Captain T Cell has the potential to become a global leader in the development of novel oncology drugs," said Dr. Jaromir Zahrádka, Managing Partner of i&i Bio.

"T cell-based immunotherapies represent a powerful tool in the challenging fight against solid tumors. We believe Captain T Cell is positioned at the forefront of cancer therapy with its unique toolbox technology approach," said Hao Nam Nguyen, Investment Manager at Brandenburg Kapital. "Brandenburg Kapital looks forward to supporting the highly ambitious team at Captain T Cell and to bringing this very promising project to fruition together with our co-investors and the BMBF funding from the GO-Bio program."

"Captain T Cell combines a powerful proprietary drug development platform with an advanced preclinical product pipeline," commented Dr. Friedrich Hillebrand, Managing Director of HIL-INVENT. "The Company’s programs address a high unmet medical need in the treatment of aggressive solid tumors. We are therefore pleased to participate in the Company’s seed financing round and support its future growth."