On December 6, 2023 Marengo Therapeutics, Inc., a clinical-stage biotech company pioneering a new way to activate T cells by targeting germline-encoded alleles in the β chain of the T cell receptor (TCR) to selectively activate the right T cell subsets to fight cancer, reported that its lead program, STAR0602, is the subject of an article published in the latest edition of Science Translational Medicine (Press release, Marengo Therapeutics, DEC 6, 2023, View Source [SID1234638206]).

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The publication, titled "A T cell receptor β chain-directed antibody fusion molecule activates and expands subsets of T cells to promote antitumor activity," highlights the potent and durable anti-tumor activity of STAR0602 across a broad range of PD1-refractory murine and human solid tumor models via a mechanism that is distinct to checkpoint inhibitors and cytokine therapies. Lead authors on the publication are Jonathan Hsu, M.Sc., Principal Scientist at Marengo, and Renee Donahue, from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).

"The comprehensive data reported in our Science Translational Medicine publication underscore the potential of Marengo’s broad STAR platform to target and activate subsets of T cells expressing different beta chain TCRs," said Andrew Bayliffe, Ph.D., Chief Scientific Officer of Marengo. "Our studies of STAR0602 show Vβ T cells expand to create a new, much more fit population of tumor-infiltrating T cells that recognize a broader set of tumor antigens or epitopes, and we are excited for the continuation of our clinical trial and the potential for STAR0602 to help patients with checkpoint inhibitor-resistant tumors."

Through a novel bi-specific antibody-fusion molecule design, STAR0602 achieves dual boosting of T cells through the TCR and costimulatory receptors that leads to profound activation, expansion and reprogramming of Vβ6 T cells representing a specific subset of the total T cell pool. STAR0602-expanded Vβ6 T cells acquire a novel effector memory phenotype with a highly expanded TCR repertoire suggesting reinvigoration and diversification of tumor antigen-specific T cell responses.

"The biology elicited by STAR0602 through engaging the TCR in this novel way seems quite different to canonical routes of TCR activation, including anti-CD3 antibodies. The atypical memory T cell phenotype observed in preclinical models dosed with STAR0602 also seem to be quite distinct and serve to illustrate that there may be many different routes to boosting anti-tumor T cell responses," said John Wherry, Ph.D., Chair of the Department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania (UPenn), Director of the UPenn Institute for Immunology, and Co-Chair of Marengo’s Scientific Advisory Board.

In large animal studies, dosing of STAR0602 was associated with less release of proinflammatory cytokines and cytokine-related toxicities, suggesting the potential for a potent treatment option with lower risk of cytokine-related adverse effects.

"As clinicians, we have mostly immune checkpoint inhibitors and some experimental CAR-Ts to treat solid tumor patients, but only a subset of them respond, and some who respond initially then relapse." said James Gulley, M.D., Ph.D., Co-Director of the Center for Immuno-Oncology at the NCI and Clinical Director, NCI. "Having a new strategy to activate the immune system for these patients is important and currently an unmet need. STAR0602 may offer a new way to selectively activate a subset of T cells with potent antitumor activity, with the added potential to avoid the toxicity associated with activating all T cells. This unique modality of T cell activation holds significant promise for patients."

On December 6, 2023 MEDSIR reported the results from the PARSIFAL-LONG study, a 5-year extended follow-up of the PARSIFAL study on endocrine-sensitive hormone receptor-positive/HER2-negative advanced breast cancer, demonstrating the effectiveness of two combined option therapies (palbociclib-letrozole and palbociclib-fulvestrant) as first-line treatments for metastatic breast cancer (Press release, MedSIR, DEC 6, 2023, View Source;advanced-breast-cancer-302007622.html [SID1234638205]). With a median follow-up of 59.7 months, the study found no significant differences in progression-free survival and overall survival when palbociclib was paired with either letrozole or fulvestrant. Given that there was no difference between groups, they were combined, and it was determined that the median progression-free survival was 33.2 months (95%CI, 27.7-39.5), and the median overall survival was 65.4 months (95%CI, 57.8-72.0).

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PARSIFAL explored the optimal endocrine agent (letrozole vs fulvestrant) to combine with palbociclib in patients with untreated, endocrine-sensitive, hormone receptor positive/HER2-negative advanced breast cancer in the first-line setting. The trial failed to demonstrate an improvement in progression-free survival of palbociclib-fulvestrant over palbociclib-letrozole, with a median follow-up of 2.7 years. At data cutoff, overall survival data were immature.

PARSIFAL-LONG extended the efficacy assessment of the PARSIFAL study with a median follow up of 5.0 years. It included a total of 389 patients, which represents 80.5% of all patients initially enrolled in PARSIFAL. Among them, 86 patients (22.1%) had a progression within the first year of treatment (early progressors), with a median overall survival of 24 months. The remaining 303 patients (77.9%) were progression-free on palbociclib-based regiments at 12 months and showed an improved median overall survival of 81.5 months.

Patients who experienced a progression during the 5-year follow-up were then assessed based on the time that they progressed. Those who progressed within the first year had an overall survival of 18 months compared to 27 months for patients that progressed after a year (hazard ratio, 0.67, 95%CI, 0.51-0.90, p=0.007), indicating that early progression (<12 months) on a palbociclib-based regimen is a strong predictor for overall survival.

These results were presented at the 46th annual San Antonio Breast Cancer Symposium by Dr. Antonio Llombart-Cussac, Head of the Oncology Department at Arnau de Vilanova Hospital and Medical Senior Scientific Lead at MEDSIR, a Spanish company specialized in the strategic design of independent clinical research. This year, MEDSIR had a significant participation at the conference by showcasing 5 studies including PARSIFAL-LONG, DEBBRAH, ATRACTIB, PARALEAL and MiRaDor. He emphasized, "Upon combining the two arms, our overall survival and progression-free survival values align comparably with other CDK4/6 inhibitors." Dr. Llombart-Cussac further noted, "Early progression with a palbociclib-based regimen serves as a robust early clinical biomarker for survival."

A total of 389 patients from 32 of the original 47 sites participated in this trial, which is the only study for a CDK4/6 regimen that recruited patients exclusively across European countries including Spain, France, Italy, Great Britain, Deutschland and Czech Republic.

The PARSIFAL-LONG study provides valuable insights, expanding the understanding of the magnitude of benefit and further reinforces the evidence supporting palbociclib in combination with endocrine therapy as a first-line treatment for patients with hormone receptor-positive/HER2-negative metastatic breast cancer.

ABOUT PARSIFAL-LONG

PARSIFAL-LONG, is a 5-year extended follow-up of the PARSIFAL study. In this analysis, the primary goal was to assess the overall survival, or the time from enrollment to death from any cause, between the two groups (palbociclib-letrozole vs palbociclib-fulvestrant). In addition, the study assessed the extended progression-free survival (time from randomization until the disease getting worse), the overall survival from the combined groups, and the post progression effectiveness or the how well the treatment worked in terms of the time from disease worsening after the first treatment to the passing of any cause. As exploratory analysis, this extended follow-up also aimed to determine if having an early progression (the disease getting worse in under 12 months while on treatment) could be an indicator of resistance to therapy.

ABOUT BREAST CANCER

Breast cancer is the second most common cause of death from cancer in women in the United States. Metastatic breast cancer causes the vast majority of deaths from the disease. In 2023, it is estimated that there will be 297,790 new cases of female breast cancer. The breast cancer subtype HR[+]/HER2[-], whose tumors express hormone receptors (HR[+]), but do not express HER2 protein (HER2[-]), is the most common subtype with an age-adjusted rate of 87.2 new cases per 100,000 women, based on 2016–2020 cases, according to the US National Cancer Institute.

On December 6, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported positive topline results from the Phase II OPALESCENCE investigator-initiated trial (IIT) of its carbonic anhydrase IX (CAIX)-targeting positron emission tomography (PET) imaging candidate, TLX250-CDx (89Zr-DFO-girentuximab), in patients with triple negative breast cancer (TNBC) (Press release, Telix Pharmaceuticals, DEC 6, 2023, View Source [SID1234638204]). Results will be presented today at the 2023 San Antonio Breast Cancer Symposium (SABCS).

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The pilot prospective study of twelve (12) metastatic patients demonstrated the expression of CAIX in TNBC and effective targeting with radiolabelled girentuximab:

Expression and targeting of CAIX in lesions in the breast, skin, adrenal gland and brain was 100%
Expression in nodes and bone was 88.0% and 91.9%, respectively
TLX250-CDx was found to be safe and well tolerated by patients.
The OPALESCENCE study (ClinicalTrials.gov ID NCT04758780) was undertaken by Dr. Caroline Rousseau at the Institut de Cancérologie de l’Ouest (ICO) in St Herblain (France). The primary objective was to evaluate how CAIX-targeted imaging with PET can be utilised for the diagnosis and staging of TNBC and to develop a deeper understanding of CAIX as a potential therapeutic target in this patient population where there is significant unmet medical need.

Results demonstrate the ability of TLX250-CDx to detect lesions that may resist chemotherapy and have a more aggressive profile resulting from hypoxia. The theranostic potential for girentuximab in this poor prognosis disease supports Telix’s goal to expand its CAIX program into other indications beyond renal (kidney) cancer, including future applications for lutetium-177 (177Lu) and actinium-225 (225Ac) based therapies.

Principal Investigator for the OPALESCENCE study, Dr. Caroline Rousseau stated, "We are pleased to present encouraging topline results from this study of Telix’s investigational CAIX targeting imaging agent in TNBC at SABCS, the largest and most prestigious scientific gathering on breast cancer research worldwide. Telix’s imaging agent TLX250-CDx, which has shown high sensitivity and specificity in clinical trials for the detection of clear cell renal cell carcinoma,[1] has now also exhibited potential utility in this most aggressive form of breast cancer, which is often metastatic and drug-resistant, with limited therapeutic options."

Dr. Christian Behrenbruch, Managing Director and Group CEO added, "Identifying new targets and treatment strategies for TNBC is a severe unmet need where only 20 percent of diagnosed patients are currently eligible for PD-L1-targeted therapies,[2] the standard of care, with the remainder reliant on toxic chemotherapeutic regimens. This topline imaging data may demonstrate proof of concept for future therapeutic applications of radiolabelled girentuximab based on a "theranostic" approach. Telix looks forward to continuing to support the development of its CAIX-targeting antibody-based program for patients with TNBC and other solid tumours, with the ultimate aim to establish CAIX as pan-cancer therapeutic target."

About Triple Negative Breast Cancer

Breast cancer is the most common cancer in women and the second most common cancer overall.[3] In 2020, over 2.2 million women were diagnosed with breast cancer and 685,000 died from their disease.[4] Triple negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers with the term triple negative referring to the fact that the cancer cells do not have any of the three markers commonly found on breast cancer cells – the oestrogen and progesterone receptors, and HER2 protein. TNBCs differ from other types of invasive breast cancer in that they grow and spread faster, have limited treatment options, and a poorer prognosis.

On December 6, 2023 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported new and updated positive results from the Phase 1 clinical trial of its breast cancer vaccine (Press release, Anixa Biosciences, DEC 6, 2023, View Source [SID1234638203]). The trial is being conducted in collaboration with Cleveland Clinic with funding by a grant from the U.S. Department of Defense.

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The data were presented at the 2023 San Antonio Breast Cancer Symposium by G. Thomas Budd, M.D., staff physician at Cleveland Clinic Cancer Institute and principal investigator of the study, in a poster entitled "Phase I Trial of alpha-lactalbumin vaccine in high-risk operable triple negative breast cancer (TNBC) and patients at high genetic risk for TNBC."

Patients who had been curatively treated for TNBC received three vaccinations given once every two weeks. IFNγ and IL-17, which are T cell immune response indicators (cellular immunity), and antibody production (B cell humoral immunity) were measured to evaluate the vaccination effect. Data from the 16 patients treated to date showed that:

The majority of patients developed ELISpot (T-cell) responses that met the rigorous protocol-specified definition of an immune response, with a measurable but lesser magnitude of response noted in the remaining patients.
12 (75%) of the women had antigen-specific IFNγ and/or IL-17 ELISpot responses that were observed at all dose levels, while ELISA antibody responses were observed at Dose Level 2 and higher.
A statistically significant (P = 0.03) increase in IFNγ over baseline (Day 0) was observed by Day 56; while a significant (P = 0.0001) increase in IL-17 over baseline was observed by Day 14.
Among the doses studied, Dose Level 1 (10 mcg α-lactalbumin/10 mcg zymosan) was determined to be a usable immunologic dose as well as the maximum tolerated dose (MTD).
No significant side effects were observed, at the MTD, besides irritation at the sites of injection. No myalgias, flu-like symptoms, or aberrant laboratory values were noted.
Anixa and Cleveland Clinic plan to investigate additional intermediate dose levels and continue studying the vaccine’s safety and immunologic effects in two additional patient cohorts.

The first cohort, which opened for enrollment in August 2023, is evaluating the combination of the Company’s breast cancer vaccine with Keytruda (pembrolizumab) in post-operative patients found to have residual disease following neoadjuvant chemo-immunotherapy.
The second cohort will investigate the safety and immunologic effects of the vaccine in patients who are BRCA1, BRCA2, or PALB2 mutation positive and are planning prophylactic risk-reducing mastectomies.
"The data from our Phase 1 trial to date has exceeded our expectations, and we are pleased with our progress. This vaccine is designed to direct the immune system to destroy TNBC cancer cells through a mechanism that has never previously been utilized for cancer vaccine development," stated Dr. Amit Kumar, Chairman and CEO of Anixa Biosciences. "We look forward to reviewing additional data as the trial continues to completion, and we are in the planning stages of the Phase 2/3 studies of this vaccine. Our goal is to initially evaluate the vaccine’s ability to prevent recurrence of cancer in survivors, and continue with extension studies to eventually determine its effectiveness in preventing the initial onset of TNBC."

"There is a large unmet need for preventing TNBC, an aggressive form of breast cancer with few targeted treatment options available," said Dr. Budd, Cleveland Clinic. "We are encouraged by the data gathered to date and look forward to determining the optimal vaccine dose in additional patient cohorts. Our hope is that future studies will demonstrate that the antigen-specific T cell responses we observed translate to the prevention of breast cancer recurrence."

Anixa is the exclusive worldwide licensee to the novel breast cancer vaccine technology invented at Cleveland Clinic, the site of the Phase 1 trial. The grant from the U.S. Department of Defense was made directly to Cleveland Clinic.

Conference Call Information

Anixa is pleased to invite all interested parties to participate in a conference call, during which this new data will be discussed.

Conference Call Details:

Presentation host:

Anixa management, with special guest speakers

Date and time:

Today, December 6, 2023, at 6:30 p.m. ET

Phone access:

Registration Link to receive your dial-in number and unique PIN

Webcast:

Available at www.anixa.com under "Events & Presentations"

About Triple-Negative Breast Cancer
One in eight women in the U.S. will be diagnosed with an invasive breast cancer at some point in their lives. Approximately 10-15% of those diagnoses are TNBC, however TNBC accounts for a disproportionately higher percentage of breast cancer deaths and has a higher rate of recurrence. This form of breast cancer is twice as likely to occur in African-American women, and approximately 70% to 80% of the breast tumors that occur in women with mutations in the BRCA1 genes are triple-negative breast cancer.

On December 6, 2023 Synaffix B.V., a Lonza company (SIX: LONN) focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index, reported the expansion of its licensing agreement with Innovent Biologics (Innovent), Inc. (HKEX:01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases (Press release, Innovent Biologics, DEC 6, 2023, View Source [SID1234638202]).

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Building on the core value proposition of Synaffix ADC technology – to enable best-in-class efficacy and tolerability for ADCs – the expanded deal with Innovent focuses on at least one new ADC candidate. This builds on a previous agreement signed in June 2021, which granted Innovent rights to deploy Synaffix’s ADC technologies on a target-specific, non-exclusive basis, including GlycoConnect, HydraSpace and one of its toxSYN linker-payloads, for a therapeutic molecule (Innovent R&D code: IBI343, a CLDN18.2 ADC) which has advanced to Phase 1 clinical development.

Under the terms of the expanded agreement, Innovent will be responsible for the research, development, manufacturing and commercialization of new ADC candidates. Synaffix is eligible to receive an upfront payment plus potential milestone payments and royalties on commercial sales for each licensed target.

Peter van de Sande, Head of Synaffix, said: "With its focus on innovative medicines and R&D expertise, Innovent has proven to be an ideal partner for us. Our partnership with Innovent has rapidly built momentum around IBI343 and we look forward to expanding our collaboration using our technology platform, including enabling off-the-shelf conversion of antibodies into ADCs, and Innovent’s world-leading clinical development capabilities with its strong proven track record to swiftly advance product candidates to the clinic."

Dr. Kaijie He, Vice President of Cancer Biology and ADC Research at Innovent, said: "Innovent has progressed one ADC candidate under the initial phase of our collaboration with Synaffix to the clinical development stage. This expanded deal adds additional novel ADC to our research projects, allowing us to further build on our understanding of ADC research and ADC pipeline development."