On October 3, 2024 OS Therapies (NYSE American: OSTX) ("OS Therapies" or "the Company"), a clinical-stage immunotherapy and Antibody Drug Conjugate biopharmaceutical company, reported that the last patient (Patient #41) enrolled in the AOST-2121 clinical trial (NCT04974008) of OST-HER2 in recurred, resected Osteosarcoma (OS) has completed their final radiographical evaluation at 52 weeks and the treatment period for the clinical trial has now ended (Press release, OS Therapies, OCT 3, 2024, View Source [SID1234647022]). The Company is preparing to request a Type C Meeting with the U.S. Food & Drug Administration (FDA) and to make any protocol adjustments based on FDA’s recommendations. Following those adjustments, the Company will lock the clinical trial database in preparation for data analysis and topline data readout, expected to be announced in the fourth quarter of 2024.

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Concurrent with this announcement the Company announces that it will be ringing the closing bell at the New York Stock Exchange today. Company President and CEO Paul Romness is scheduled to give two interviews live on national television networks:

"B" Block in Market Movers on Fintech.TV at 9:10am on Thursday, October 3, 2024
Trading 360 on the Schwab Network at 11:30am on Thursday, October 3, 2024
OST-HER2, a biologic therapeutic candidate, is a Lm (Listeria monocytogenes) vector-based off-the-shelf immunotherapeutic vaccine designed to prevent metastasis, delay recurrence, and increase overall survival in patients with Osteosarcoma. The AOST-2121 Phase 2b clinical trial of 41 patients treated with OST-HER2 at 21 clinical trial sites across the United States is designed to demonstrate efficacy in patients who have already had recurrent metastatic disease to the lungs and are highly likely to continue to recur. A total of 16 OST-HER2 doses were administered once every three weeks, with a follow-up approximately four weeks after the final dose was administered, for a total of 52 weeks on study. Radiographic evaluation of recurrence occurred throughout the treatment period. The primary endpoints for the AOST-2121 study are Event Free Survival ("EFS"), defined as absence of recurrence of primary tumor or metastasis) at 12 months and Overall Survival (OS) at 36 months, with interim OS endpoints at 12 months, 18 months and 24 months. Topline EFS data, interim OS data, as well as additional secondary data analyses are expected to be reported in the fourth quarter of 2024.

The proposed OST-HER2 mechanism of action is based on innate and adaptive immune stimulating responses activated by the Lm vector. This treatment generates T-cells that can eliminate or slow potential micro-metastases that can grow into recurrent Osteosarcoma. T-cell responses target HER2 expressed by the tumor and then kill the cell, releasing additional tumor targets. There are currently no approved adjuvant treatments for recurrent Osteosarcoma in the United States. There have not been any novel therapeutic interventions approved by the FDA in over 40 years.

On October 3, 2024 AstraZeneca reported that supplemental New Drug Application (sNDA) for Calquence (acalabrutinib) has been accepted and granted Priority Review in the US for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) (Press release, AstraZeneca, OCT 3, 2024, View Source [SID1234647007]).

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The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2025.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), resulting when B-lymphocytes mutate into malignant cells within a region of the lymph node known as the mantle zone.2,3 The disease is often diagnosed at advanced stages and remains largely incurable. It is estimated that there are more than 27,500 people living with MCL worldwide.4,5

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Today’s Priority Review acceptance reinforces the potential of Calquence to transform outcomes in untreated mantle cell lymphoma. Data from the ECHO trial showed Calquence plus chemoimmunotherapy significantly delayed disease progression and showed a trend to improved survival in patients with this currently incurable blood cancer. We are working closely with the FDA to provide patients this potential new treatment as soon as possible."

The sNDA is being reviewed under Project Orbis, an initiative of the FDA which provides a framework for concurrent submission and review of oncology medicines among participating international partners to bring cancer treatments to patients around the world as early as possible.

Results from the ECHO Phase III trial recently were presented during the late-breaking oral session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress.

In the trial, Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care (SoC) chemoimmunotherapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94; p=0.016). The addition of Calquence to SoC provided almost 1.5 years of additional median progression free survival (mPFS) with mPFS of 66.4 months for patients treated with the Calquence combination versus 49.6 months with SoC.

Overall survival (OS) showed a favourable trend for the Calquence combination compared to SoC chemoimmunotherapy (HR 0.86; 95% CI 0.65-1.13; p=0.2743). The OS trend was sustained over time, although most patients in the SoC arm who needed subsequent therapy received a BTK inhibitor, mainly Calquence. The OS data were not mature at the time of this analysis, and the trial will continue to assess OS as a key secondary endpoint.

The ECHO trial was conducted during the COVID-19 pandemic, and 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 FDA. After censoring for COVID-19 deaths, the PFS was further improved in both arms, with the Calquence combination reducing the risk of disease progression or death by 36% (HR 0.64; 95% CI; 0.48-0.84; p=0.0017). A favourable trend was seen for OS in this analysis for the Calquence combination, but OS data were not mature at the time of this analysis (HR 0.75; 95% CI 0.53-1.04; p=0.0797).

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

Notes

MCL
While MCL patients initially respond to treatment, patients do tend to relapse.6 MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it is estimated that approximately 4,000 new patients are diagnosed with MCL each year.6,7

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.8 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.8

The primary endpoint is PFS assessed by an Independent Review Committee; other efficacy endpoints include OS, overall response rate (ORR), duration of response (DoR) and time to response (TTR).8 The trial was conducted in 27 countries across North and South America, Europe, Asia and Oceania.8

The ECHO trial enrolled patients from May 2017 to March 2023, continuing through the COVID-19 pandemic. Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.9

Calquence
Calquence (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.10 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence has been used to treat more than 85,000 patients worldwide11 and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL. Calquence is also approved in the US, China and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.

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.

On October 3, 2024 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported to gather clinical evidence for the steady improvement of its AI-Immunology platform (Press release, Evaxion Biotech, OCT 3, 2024, View Source [SID1234647026]).

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The platform’s precision has significantly improved between the two clinical trials with Evaxion’s personalized cancer vaccine EVX-01. In the ongoing phase 2 trial, 81 out of 103 (79%) vaccine targets assessed to date triggered a tumor-specific immune response, a notable increase from the 58% observed in the phase 1 trial completed last year.

The high number of immune-active vaccine targets is observed across all patients. The ability to trigger a broad and consistent tumor-specific immune response is pivotal for a vaccine’s clinical efficacy and, thereby, critical for the vaccine’s commercial potential and ability to address unmet medical needs.

"As a truly AI-first TechBio company, Evaxion rests on our leading AI-Immunology platform and its continued improvement remains a top priority for us. It is, of course, very pleasing to see that we are successful in that work, reaching 79% of identified vaccine targets triggering an immune response in the ongoing EVX-01 phase 2 trial. This compares very favorably to data reported from other personalized cancer neoantigen trials. We are further pleased that the clinical outcome data are also very strong, providing us with a compelling AI-Immunology derived investigational vaccine candidate." says Christian Kanstrup, CEO of Evaxion.

The improvement of the AI-Immunology platform’s predictive capabilities results from iterative learning loops, optimization based on clinical data and the integration of novel bioinformatic and machine learning methodologies.

About AI-Immunology
AI-Immunology is a scalable and adaptable artificial intelligence technology platform at the forefront of vaccine discovery for infectious diseases and cancers. By integrating the collective power of proprietary AI models PIONEER, EDEN, RAVEN, and ObsERV, the platform can model the complexity of the patient’s immune system. AI-Immunology advanced computational modeling swiftly and uniquely identifies, predicts, and designs vaccine candidates, revolutionizing the landscape of immunotherapy by offering a holistic and personalized approach to combat fast-evolving pathogens and malignant cells.

On October 2, 2024 Alentis Therapeutics ("Alentis"), the clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, reported that the U.S. Food & Drug Administration (FDA) cleared an IND application for ALE.P02, an anti-CLDN1 ADC with a tubulin inhibitor payload (Press release, Alentis Therapeutics, OCT 2, 2024, View Source [SID1234646996]). A Phase 1/2 clinical trial in patients with CLDN1+ squamous tumors is expected to start during the first quarter of 2025.

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"ADCs have shown great potential in the treatment of cancer," Luigi Manenti, Chief Medical Officer of Alentis. "Squamous cancers originating in the head and neck, cervix, esophagus and lung are characterized by high CLDN1 expression, and ALE.P02 provides a first-in-class opportunity for these patients who need new therapies after first-line treatment fails."

"Anti-CLDN1 ADCs are exciting because they address the urgent need for novel targets in the ADC space," added Tony Mok, Professor of Clinical Oncology at the Chinese University of Hong Kong. "ALE.P02 is particularly promising for squamous cancers, including HNSCC and NSCLC, where CLDN1 is often overexpressed. The unmet medical need in these indications is significant, and I look forward to the results of the Phase 1/2 study."

Dr. Roberto Iacone, Chief Executive Officer of Alentis said, "ALE.P02, entering the clinic, marks a significant advancement in our oncology pipeline. We can maximize our development plan by leveraging insights from human clinical trials of lixudebart (ALE.F02), used as the backbone antibody for Alentis’ ADCs."

Dr. Iacone added, "For our second ADC program, ALE.P03, with its topoisomerase I inhibitor payload, we plan to initiate a first-in-human clinical trial in 2025."

About ALE.P02
ALE.P02 is a first-in-class ADC designed by linking a tubulin inhibitor, a potent cancer drug, to our antibody that specifically targets a unique CLDN1 epitope exposed on cancer cells. This combination could be a powerful new tool to fight the many squamous cancers that overexpress CLDN1 with less toxicity than traditional cancer drugs.

On October 2, 2024 Etcembly reported a groundbreaking new research study aiming to uncover new targets for cancer therapies by analysing the immune cells of cancer survivors (Press release, Etcembly, OCT 2, 2024, View Source [SID1234646997]).

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The ETCh study is recruiting people aged 18-65 who are living with or have survived cancer to join the study, as well as healthy volunteers. Participants will be asked to donate a small amount of blood up to five times over the course of one year, and provide information about their health.

Unlocking the secret to surviving cancer

The ETCh study is rooted in the well-established concept that long-term survivors have beaten cancer due to their immune system’s ability to recognise and eliminate cancerous cells. However, a systematic search for the specific targets recognised within tumours has yet to be undertaken.

In this study, blood samples will be collected from people who are living with or have survived cancer as well as healthy individuals. The research team will conduct an extensive analysis of the immune repertoire at an unprecedented scale by sequencing millions of antibodies and T cell receptors (TCRs) from each participant.

Etcembly’s advanced AI platform, EMLyTM, will then perform an in-depth analysis to identify which of these are likely to play a role in recognising and destroying cancer cells, and determine the aberrant molecules in tumours that they target.

These molecules could become new targets for next-generation immunotherapies that harness the power of a patient’s own immune system to combat cancer. The team expects to identify new targets within 12 to 18 months, which will then enter Etcembly’s pipeline for developing novel TCR-based therapies.

Harnessing the power of TCRs

This approach will allow Etcembly to delve deep into the immune response of cancer survivors and find vital clues to future cures.

Nick Pumphrey, Chief Scientific Officer at Etcembly says, "There is an urgent need to discover new cancer targets that traditional approaches have largely failed to deliver. By approaching the problem from the opposite direction, we can identify TCRs and targets from cancer survivors that have proven their ability to beat cancer, allowing us to develop therapies that are more likely to work for others."