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Immorta Bio to Present SenoVax™ Cancer Senolytic Immunotherapy Preclinical Data at American Association of Immunologists Meeting

On May 5, 2025 Immorta Bio Inc, a scientific longevity company dedicated to "Treating Diseases of Aging and Treating Aging as Disease", reported a talk called "Immunologically Mediated Senolysis" at the "Clinical Immunology Symposium" of the American Association of Immunologists Annual Meeting (Press release, Immorta Bio, MAY 5, 2025, View Source [SID1234652528]). Immorta Bio’s talk will be accompanied by presentations from Pfizer1 and University of Pittsburgh2. The talk will occur Monday, May 5 | 8:15 AM – 10:15 AM | Room 316C at the Hawai’i Convention Center.

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Immorta Bio is the first company to develop a "senolytic immunotherapy" for treatment of cancer and aging. This treatment comprises of training the immune system of patients to selectively kill "senescent cells" that promote aging and act as a shield to protect cancer against immune responses. By removing this defense mechanism, cancer becomes susceptible to immune attack.

The Company has shown that its lead senolytic immunotherapy product, SenoVax, is capable of destroying lung, breast, pancreatic and brain cancers, as well as melanoma3 in animal models.

"Having been chosen to present our work on using the immune system to fight cancer and aging in such an esteemed panel is truly an honor," said Dr. Thomas Ichim, President and Chief Scientific Officer of Immorta Bio.

T cell mediated mechanisms of how SenoVax enables its anticancer effects have previously been published in the peer-reviewed literature with collaborators at University of California San Diego, Georgetown University, Ceders Sainai, and Calidi Bio4. Additionally, the Company recently demonstrated that natural killer cell activation as a result of SenoVax therapy also plays a role in stimulation of cancer destruction5.

"We have founded Immorta Bio on the principle of ‘Scientific’ Longevity," said Dr. Boris Reznik, President and CEO of Immorta Bio. "There is no better validation of our science than to be chosen to give an oral presentation at such a prestigious and exclusive scientific gathering as AAI2025."

Genezen and Optieum Biotechnologies Partner to Support cGMP Manufacturing of Groundbreaking CAR-T Therapy for Glioblastoma

On May 5, 2025 Genezen, a leading viral vector Contract Development and Manufacturing Organization (CDMO), and Optieum Biotechnologies, Inc. (Optieum), a preclinical stage company dedicated to the discovery and development of innovative CAR-T cell therapies, reported a partnership for cGMP manufacturing of the lentiviral vector (LVV) construct used in the production of OPTF01, a novel CAR-T therapy for glioblastoma treatment (Press release, Genezen, MAY 5, 2025, View Source [SID1234652527]).

Derived from Optieum’s proprietary Eumbody System, OPTF01 specifically targets Fibroblast activation protein-alpha (FAPα), a protein expressed on both tumor cells and the surrounding pericytes and Cancer-associated Fibroblasts (CAFs). Hence, OPTF01 can potentially disrupt the immunosuppressive microenvironment around the tumor while simultaneously attacking the malignant cells within the tumor. Successful development of this therapeutic approach would address a critical unmet medical need for patients with refractory glioblastoma who currently face limited treatment options with poor prognoses, as well as various other solid tumor indications.

Under this collaboration, Genezen will provide the technology transfer, process development, and cGMP manufacturing of the LVV construct used in the onward production of the OPTF01 CAR-T product. "Genezen is honored to support Optieum’s best-in-class CAR-T programs with our best-in-class LVV expertise to bring these critical therapies to life," said Steve Favaloro, Chairman and CEO of Genezen. "This collaboration with Optieum underscores our rich experience and the capabilities of both our people and state-of-the-art facilities to support customers on a global scale – now including a leading Japanese biotech."

Shun Nishioka, CEO of Optieum added, "At Optieum, we are committed to redefining the future of CAR-T therapy through relentless innovation and scientific rigor. Partnering with Genezen’s team of experts ensures that critical materials for our groundbreaking therapies are manufactured to the highest standards, accelerating our progress toward delivering next-generation therapies for glioblastoma and other solid tumors."

OPTF01 is derived from the Eumbody System, a proprietary platform representing a significant advancement in CAR-T cell therapy development. This platform leverages rapid and expansive functional screening to identify and optimize CAR constructs in unprecedented fashion. By dynamically harmonizing single-chain variable fragment (scFv) sequences to enhance the functional capabilities of T cells, the Eumbody System sets a new standard in CAR-T innovation.

Phanes Therapeutics announces first patient dosed in clinical study of peluntamig in combination with atezolizumab

On May 5, 2025 Phanes Therapeutics, Inc. (Phanes), a clinical stage biotech company focused on innovative drug discovery and development in oncology, reported that the first patient has been dosed in the clinical study of peluntamig in combination with Roche’s anti-PD-L1 monoclonal antibody atezolizumab (TECENTRIQ ) (Press release, Phanes Therapeutics, MAY 5, 2025, View Source [SID1234652526]). The study is being conducted in a cohort of patients with extensive-stage small cell lung cancer (ES-SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), or extrapulmonary neuroendocrine carcinomas (EP-NECs).

As previously announced, Phanes is conducting this study under a clinical supply agreement with Roche. Peluntamig is Phanes’ first-in-class native IgG-like bispecific antibody (bsAb) targeting DLL3 and CD47. It was granted two orphan drug designations by the FDA for the treatment of SCLC and NEC, respectively, and two Fast Track designations for ES-SCLC with disease progression following platinum chemotherapy with or without a checkpoint inhibitor, and metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC), respectively.

The multi-center Phase I/II clinical trial of peluntamig (NCT05652686), known as the SKYBRIDGE study, is currently evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy of peluntamig in patients with advanced or refractory cancers expressing DLL3. A Phase I clinical trial of peluntamig is also ongoing in China (CTR20242720), and a Phase II clinical trial has been approved in China.

TECENTRIQ (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

CStone Presents the Latest Preclinical Findings of CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody) at 2025 AACR

On May 5, 2025 CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on anti-cancer therapies, reported that a poster presentation of preclinical data of CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody), a key asset in CStone Pipeline 2.0, has been delivered at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, CStone Pharmaceauticals, MAY 5, 2025, View Source [SID1234652525]). CS2009 global phase I trial is ongoing in Australia with first patient dosed in this March and will soon be expanded to China and the US.

PD-1, VEGFA, and CTLA-4 are clinically validated targets for immunotherapies, which can exert complementary, multi-dimensional anti-tumor effects through synergistic mechanisms. Blockade of PD-1 and CTLA-4 has demonstrated synergistic effects, extending overall survival benefits as well as progress-free survival benefits in many tumor types including NSCLC, which could be further strengthened by the blockade of VEGFA signaling. By integrating these three mechanisms of actions in one molecule, CS2009 holds great potential to deliver superior clinical benefits over PD-(L)1 antibodies or PD-(L)1/VEGF and PD-(L)1/CTLA4 bispecific antibodies.

CS2009 is a promising trispecific antibody targeting PD-1, VEGFA, and CTLA-4, which demonstrates broad clinical application prospects for solid tumors with the great potential to become the next-generation immune-oncology backbone to replace current anti-PD-(L)1-based therapies.

Key Highlights:

CS2009 exhibited enhanced affinity upon simultaneous PD-1/CTLA-4 engagement. CS2009 enhances anti-tumor efficacy by preferentially targeting PD-1/CTLA-4 double positive T cells in TME.
CS2009 exhibited an approximately 150-fold enhancement in checkpoint inhibitory activity on PD-1/CTLA-4 dual-reporter assay through crosslinking with VEGFA dimers. In PD-1 reporter assay, the CS2009/VEGFA combination demonstrated approximately 300-fold greater immune checkpoint activity compared to CS2009 alone. Mixed lymphocyte reaction (MLR) assays evaluating primary T cell activation revealed that crosslinking with VEGFA dimer significantly increases the activity of CS2009. These findings indicate enhanced activity of CS2009 in VEGFA-enriched TME and minimized peripheral overactivation-induced immune-related toxicity, thereby expanding its therapeutic window.
CS2009 demonstrated dose-dependent T-cell activation during GLP-toxicity study in cynomolgus monkeys.
CS2009 exhibited comparable pharmacokinetic (PK) profiles to those of monoclonal antibodies.
CS2009 demonstrates superb tolerability with the highest non-severely toxic dose (HNSTD)/ the no observed adverse effect level (NOAEL) identified as 100 mg/kg.
In summary, CS2009 is a trispecific antibody targeting PD-1, VEGFA, and CTLA-4, with the potential to be first- or best-in-class for major tumor types. Its differentiated molecular design combines three clinically validated targets, preferentially invigorating exhausted tumor infiltrating lymphocytes (TILs) while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including but not limited to non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer. Our results show that CS2009 exhibits superior anti-tumor activity compared to potential competitors, including PD-(L)1/CTLA-4 bispecific antibodies, PD-(L)1/VEGF bispecific antibodies, and PD-(L)1/CTLA-4 combination therapies.

Poster Information:

Title: CS2009: A first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFA with potential to be a next-generation backbone therapy with combined checkpoint inhibition and anti-angiogenesis
Session Title: Overcoming Checkpoint Inhibition and Tumor Suppression
Abstract Number: 7299
Date & Time: Wednesday, April 30, 2025, 9:00 AM – 12:00 PM ET
Location: Poster Section 39, Board #14

Calquence plus chemoimmunotherapy approved in the EU as first and only BTK inhibitor for 1st-line mantle cell lymphoma

On May 5, 2025 AstraZeneca reported that Calquence (acalabrutinib) in combination with bendamustine and rituximab has been approved in the European Union (EU) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are not eligible for autologous stem cell transplant (Press release, AstraZeneca, MAY 5, 2025, View Source [SID1234652524]).

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and was based on positive results from ECHO Phase III trial, presented at the European Haematology Association (EHA) (Free EHA Whitepaper) 2024 Congress and published in The Journal of Clinical Oncology, which demonstrated that Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94; p=0.016). Median progression-free survival (PFS) was 66.4 months for patients treated with the Calquence combination versus 49.6 with chemoimmunotherapy alone.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma, often diagnosed at an advanced stage.1,2 An estimated 6,000 patients were diagnosed with MCL in the UK, France, Germany, Spain and Italy in 2024.3

Martin Dreyling, MD, Department of Medicine, University Hospital LMU Munich, and investigator in the trial, said: "This approval provides a new first-line treatment option for patients in the EU with mantle cell lymphoma, an aggressive lymphoma with a dismal long-term outcome still today. With a progression-free survival improvement of more than 16 months for these patients, the acalabrutinib combination is a much-needed advance in this challenging disease."

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "Treatment with the Calquence combination in first-line mantle cell lymphoma demonstrated a significant improvement in progression free survival and a consistent safety profile for patients in the pivotal ECHO trial. As the first and only BTK inhibitor approved in this indication in the EU, we are proud to provide a much-needed new option to patients living with this difficult disease."

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

Calquence plus bendamustine and rituximab is approved in the US and several other countries in this setting based on the ECHO results. Regulatory applications are currently under review in Japan and several other countries in this indication.

This approval follows the recent approval for Calquence monotherapy for the treatment of adult patients with relapsed or refractory MCL in the EU.

Notes
Mantle cell lymphoma (MCL)
While MCL patients initially respond to treatment, patients do tend to relapse.4 MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; It is estimated that there are more than 21,000 patients diagnosed with MCL in the US, UK, France, Germany, Spain, Italy, Japan and China.3,4,5

ECHO
ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to SoC chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=635) with previously untreated MCL.6 Patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, continuously, until disease progression or unacceptable toxicity. Additionally, all patients received six 28-day cycles of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed by rituximab maintenance for two years if patients achieved a response after induction therapy.6

The primary endpoint is PFS assessed by an Independent Review Committee; other efficacy endpoints include overall survival (OS), overall response rate, duration of response and time to response.6 The trial was conducted in 27 countries across North and South America, Europe, Asia and Oceania.6

The ECHO trial enrolled patients from May 2017 to March 2023, continuing through the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome in alignment with the FDA.

Calquence
Calquence is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.7 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US, Japan and China, and approved for CLL in the EU and many other countries. Calquence is also approved for the treatment of adult patients with previously untreated MCL in the US and other countries. It is also approved for the treatment of adult patients with MCL who have received at least one prior therapy in China and several other countries. Calquence is not currently approved for the treatment of MCL in Japan.

As part of an extensive clinical development programme, Calquence is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma.

AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care in haematology. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians.

In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across multiple scientific platforms. Our acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., pioneers of autologous cell therapies, expand our haematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end discovery, development and delivery of novel therapies.