Valerio Therapeutics Acquires Emglev Therapeutics, a Single-Domain Antibody-Based Therapeutics Company

On September 30, 2024 Valerio Therapeutics S.A. (Euronext Growth Paris: ALVIO), a clinical-stage biotechnology company leading the way in the development of innovative DNA Decoy therapeutics, reported the acquisition of Emglev Therapeutics, a spinoff of Institut Curie, one of France’s leading cancer centers (Press release, Valerio Therapeutics, SEP 30, 2024, View Source [SID1234646959]).

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Valour Bio has been established as a wholly owned subsidiary of Valerio Therapeutics to focus on discovering single domain antibodies (sdAbs) as drug and radio conjugates, bispecific T-cell engagers, blocking and binding sdAbs, or CAR-T sdAb drug candidates for multiple therapeutic areas.

Emglev’s proprietary synthetic sdAb libraries overcome the current barriers of conventional antibody discovery by providing unique targets and selecting humanized or fully human sdAbs entirely in vitro. These sdAbs are validated for a wide array of therapeutic applications, offering a distinct advantage in antibody development.

Animal free sdAb screening strategies exploit highly diverse synthetic libraries and functional screening, enabling the identification of validated lead binders in less than two months. Since Emglev’s antibody scaffold is already humanized or derived from human variable region of the heavy chain (VH), there is no need for further humanization, thereby streamlining the development process and reducing the risk of immunogenicity and loss of affinity.

Emglev’s sdAb technology has broad applications in several therapeutic areas such as inflammatory disorders, autoimmune diseases and cancer, but it also allows for the development of various treatment modalities including sdAb drug and radio-conjugates, bispecific T-cell engagers, blocking and binding sdAb or CAR-T sdAb drugs to name a few. Pre-clinical proof-of-concept of the sdAb technology has been obtained using CAR-T sdAb, BiTE sdAb and sdAb-drug conjugate, highlighting the ability of Emglev to rapidly and efficiently discover tailored antibody fragments with enhanced properties. Added to the expertise brought by Valerio Therapeutics, this positions Valour Bio with a versatile and promising platform for developing new best-in-class or first-in-class therapies for a wide range of diseases.

The acquisition is structured through a sale of shares paid in cash and a contribution in kind of Emglev shares against Valour Bio shares. As a result, shareholders of Emglev became shareholders of Valour Bio.

Dr. Shefali Agarwal, President & Chief Executive Officer of Valerio Therapeutics and CEO of Valour Bio, stated:

"The acquisition of Emglev Therapeutics through our newly formed subsidiary Valour Bio reinforces our commitment to bring innovative therapeutics to patients. We are excited to advance this next-generation technology developed by the accomplished scientists at Emglev and we look forward to the novel treatments this platform may yield like sdAb drug and radio -conjugates, bispecific T-cell engagers, blocking and binding sdAb or CAR-T sdAb drugs. Furthermore, we believe that the versatility of this platform can not only target a wide array of antigens but potentially address current limitations of antibody-based therapeutics such as tissue penetration, immunogenicity and ease of manufacturing. Following this acquisition, Valour Bio will focus on optimizing the therapeutic use of single-domain antibodies, focusing on developing treatments for severe and life-threatening diseases, including but not limited to autoimmune and inflammatory diseases as well as cancers."

Christelle Masdeu, CEO of Emglev Therapeutics, commented:

"We are excited to enter into this joint effort with Valerio Therapeutics. As a shareholder of Valour Bio now holding the Emglev platform, we remain committed to investing our energy, expertise and passion to develop unique treatments addressing unmet medical needs. The synergy created by combining Emglev’s proprietary synthetic single-domain antibody platform with Valerio’s distinctive preclinical and clinical development expertise perfectly aligns with our mission to deliver transformative therapies that make a meaningful difference in patients’ lives."

Dr. Sandrine Moutel, Emglev’s co-founder and head of the Antibody facility at Institut Curie and Dr. Franck Perez, Emglev’s co-founder and a member of its scientific board, director of the Cell Biology and Cancer Unit at Institut Curie, stated jointly:

"As founding members of Emglev, we are delighted to enter into this agreement which represents the culmination of tireless work by a dedicated team of scientists. Our team has created a platform that can generate therapeutics including CAR-Ts, T-cell engagers, binders, and bispecifics sdAbs demonstrating wide and versatile applicability to many diseases. This new chapter allows us to bring our vision of single-domain antibodies one step closer to the clinic and we are looking forward to beginning this journey with Valerio Therapeutics."

Cécile Campagne, Director of Institut Curie’s Technology Transfer Office, declared:

"We are proud of the path taken by Emglev Therapeutics, a start-up that has emerged from Institut Curie’s incubation program, which is moving forward at full speed! The acquisition of Emglev, less than two years after its creation, by Valour Bio, a subsidiary of Valerio Therapeutics which is a listed company, reflects the quality of Institut Curie’s innovations and the importance of putting them at the service of the creation of companies that will bring these cutting-edge technologies to all patients."

To this end, Valerio Therapeutics will provide Valour Bio with services in terms of scientific know-how in drug development, company support and equipment against financial compensation.

Given the potential of the technology and depth of the market potential, Valour Bio is confident that it will find the needed financial resources to support the company’s growth. The acquisition and operation of Emglev will enable new scientific and financial synergies to be created within the Valerio Group, with the first benefits for Valerio Therapeutics and Valour Bio expected to materialize in Q1 2025.

Research Study from Indivumed Therapeutics Reveals a Path for the Discovery of New Targets and Development of Novel Cancer Therapies

On September 30, 2024 Indivumed Therapeutics reported significant changes in the molecular characteristics of tumor samples within as little as 10 minutes after surgical removal (Press release, Indivumed Therapeutics, SEP 30, 2024, View Source [SID1234646957]). The findings underline the importance of rapid snap freezing of tissue samples to reliably capture cancer biology and reveal novel drug targets.

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Publishing in Cell Death & Disease, the study analyzed the impact of cold ischemia time (the time it takes to preserve surgically removed tissue) on more than 1,800 tumor and matched normal tissue samples across four cancer types: colorectal, liver and two subtypes of lung cancer.

Multi-omics analysis was used to compare gene expression, proteins, and phosphoproteins in samples with cold ischemia times ranging from less than 10 to more than 25 minutes. Significant differences emerged in the expected patterns of gene and protein activity in samples with longer cold ischemia times compared with those frozen within less than 10 minutes.

Senior Data Scientist at Indivumed Therapeutics, Silvia von der Heyde, said, "We already knew that the molecular expression profile in tissue samples changes the longer they are outside the body, but we were surprised to see the extent of the differences after just ten minutes. This misleading picture of cancer biology has a significant impact on drug discovery, leading researchers to waste time and money on false leads or simply not seeing potentially important targets for novel therapeutics."

Through its Global Clinical Network partners, Indivumed Therapeutics has gathered an unrivaled biobank of many thousands of high-quality tumor and normal tissue samples, collected and rapidly frozen within an average of 10 minutes cold ischemia time according to the company’s strict protocols.

"We’re proud to build on this unique resource, using the potential of bioinformatics, biomathematics, and cell biology to identify, validate, and characterize novel oncology drug targets." says Jobst Landgrebe, Head of R&D and Chief Technology Strategist at Indivumed Therapeutics.

This paper validates the original vision of Indivumed’s founder and CEO Hartmut Juhl, who recognized that the best way to find genuine targets for novel cancer drugs is to get as close to the molecular reality of the disease as possible.

Juhl says, "I am beyond excited to see my vision from 22 years ago reflected in our work today. Our long-standing commitment to sample and data quality is finally paying off and contributing to the search for new treatments that will bring forward the promise of effective cancer medicine for all the patients out there."

City of Hope to Present Leading-Edge Radiotherapy Treatments for People with Lung, Genitourinary and Blood Cancers at the American Society for Radiation Oncology Annual Meeting

On September 30, 2024 City of Hope, one of the largest and most advanced cancer research and treatment organizations in the U.S. and ranked among the nation’s top 5 cancer centers by U.S. News & World Report, reported that it is part of today’s press conference program at the American Society for Radiation Oncology (ASTRO) Annual Meeting, where a renowned City of Hope radiation oncologist will present phase 3 clinical trial data showing that people with limited-stage small cell lung cancer may benefit from adding immunotherapy to chemoradiation, but not if both treatments are given at the same time (Press release, City of Hope, SEP 30, 2024, View Source [SID1234646956]). The results suggest that the timing of when immunotherapy is given plays a key role in its ability to extend survival.

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"The introduction of immunotherapy marked the first significant breakthrough in treating small cell lung cancer treatment in decades. Now, we see that if you give immunotherapy concurrently with chemoradiation, it does not yield the same survival benefit as it does when we add it after standard treatment," said lead author Kristin Higgins, M.D., a radiation oncologist, clinical professor and chief clinical officer at City of Hope Cancer Center Atlanta.

Dr. Higgins is presenting the late-breaking abstract at a 10 a.m. ET press conference today in room 103A of the Walter E. Washington Convention Center in Washington, D.C.; the scientific plenary will take place at 2:10 p.m. ET in Ballroom A/B/C.

ASTRO is the world’s largest radiation oncology society, with more than 10,000 members. Radiation therapy contributes to 40% of global cancer cures, and more than 1 million Americans receive radiation treatments for cancer each year.

Lung cancer is the leading cause of cancer deaths in the U.S. An aggressive form of the disease is small cell lung cancer, which accounts for 10-15% of all lung cancers. Standard treatment for patients with limited-stage disease that has not spread outside the chest and is potentially curable includes concurrent radiation therapy and chemotherapy. While treatments can be effective initially, the cancer often recurs and options for additional treatment have historically been limited.

Dr. Higgins and her colleagues randomized 544 patients at centers across the U.S. (n=500) and Japan (n=44) to receive standard chemoradiation with or without atezolizumab immunotherapy. All patients received radiation therapy either twice daily or once daily as well as four cycles of concurrent chemotherapy. For patients on the experimental arm, atezolizumab was also given every three weeks beginning at the start of radiation, for a maximum of one year.

Contrary to expectations, concurrent treatment with atezolizumab and chemoradiation did not improve survival rates compared to standard care. The lack of survival benefit when giving immunotherapy together with chemoradiation, rather than after radiation is completed, indicates that the activity of this type of immunotherapy is reduced when given simultaneously with thoracic radiation, likely due the inherent immunosuppressive effects of radiation, Dr. Higgins explained.

"We know that radiation suppresses the immune system to a certain degree in the immediate sense, and immunotherapy relies on the immune system to be effective," she said. "Adding these drugs after you give radiation can make the immunotherapy more potent, but you have to allow the immune system time to recover to really see the two work well together."

There was a benefit to giving radiation twice daily over giving it once daily, regardless of study arm. In both groups, patients treated twice daily lived longer on average; median overall survival for those treated twice daily was 35.4 months, compared to 28.3 months for people treated once per day.

"Sometimes, if you give too much therapy at the same time, it actually yields worse outcomes. And this trial demonstrated that. But at the same time, we did see that changing the way you give radiation can help," Dr. Higgins said, noting that City of Hope continues to be at the forefront of a powerful form of immunotherapy known as chimeric antigen receptor (CAR) T cell therapy. City of Hope researchers are among the scientists working to develop and test new lung cancer immunotherapy treatments.

Other world-renowned City of Hope physicians and researchers also will present new data and offer expert perspectives on leading-edge cancer research and treatments in development.

Is biology-guided radiotherapy an option for people with prostate cancer?

Presentation time and location: Monday, Sept. 30, from 3:50 to 4 p.m. ET in Room 145

City of Hope was the first in Southern California and among the first in the nation to adopt a type of biology-guided radiotherapy called SCINTIX therapy that later in 2023 was cleared by the U.S. Food and Drug Administration. This study, led by Chunhui Han, Ph.D., City of Hope clinical professor of radiation oncology, included prostate cancer patients and resulted in the development of a comprehensive set of screening criteria to identify people who would benefit from this leading-edge, personalized radiation oncology treatment. City of Hope aims to develop efficient protocols so that other institutions one day can also implement the SCINTIX therapy on the RefleXion X1.

Phase 2 trial with leukemia patients could lead to radiotherapy that attempts to bypass harm to organs

Presentation time and location: Monday, Sept. 30, from 5:10 to 5:20 p.m. ET in Room 144

In a phase 2 trial noted as the largest prospective study using total marrow and lymphoid irradiation (TMLI), Jeffrey Wong, M.D., City of Hope professor of radiation oncology, Anthony Stein, M.D., and colleagues treated 74 patients with either acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) with TMLI, which delivers targeted radiation to bone marrow while reducing negative impact to organs. The team developed a regimen that could be an effective hematopoietic cell transplant option for AML and ALL patients with recurrent cancer or disease that has become resistant to treatment. The regimen is currently under evaluation as a potential replacement for standard total body irradiation conditioning in patients with AML who are in complete remission. City of Hope’s bone marrow and blood stem cell transplant program is the largest in the country; its doctors have performed nearly 20,000 transplants to date.

Study evaluating effectiveness of pre-transplant radiotherapy that limits toxicity to organs

Presentation time and location: Tuesday, Oct. 1, from 1:25 to 1:35 p.m. ET in Room 144

Colton Ladbury, M.D., City of Hope assistant professor of radiation oncology, led the largest study to date reporting long-term toxicities resulting from total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI), both of which are used to prepare patients for a stem cell transplant. Some 302 patients with multiple myeloma or acute leukemia were followed for up to eight years with median follow-up of 6.3 years in living patients. They found that TMI/TMLI is associated with lower rates of pulmonary toxicity, renal toxicity and hypothyroidism compared with historical cohorts treated with conventional total body irradiation.

Dr. Ladbury is one of 12 residents in the world to receive an ASTRO recognition award for his quick pitch oral. The award is designed to highlight excellence among peers at the largest annual meeting of radiation oncologists from around the globe.

A potentially better way to deliver radiotherapy and chemotherapy to people with lung cancer

Presentation time and location: Tuesday, Oct. 1, from 1:25 to 1:35 p.m. ET in Room 147

In an early-phase trial, researchers led by Percy Lee, M.D., City of Hope professor of radiation oncology, found that it is safe and effective to treat patients with locally advanced, inoperable non-small cell lung cancer using chemoradiation via a dose-escalated adaptive stereotactic ablative radiotherapy boost in 15 sessions of radiation instead of the standard 30 sessions as they also receive chemotherapy.

Using AI to evaluate immune system response

Presentation time and location: Tuesday, Oct. 1, from 1:25 to 1:35 p.m. ET in Room 152

Immuno-positron emission tomography (ImmunoPET) allows for spatial evaluation of white blood cell distributions. William Tyler Watkins, Ph.D., physicist and City of Hope associate clinical professor, led a research team that leveraged artificial intelligence (AI) to segment the human body and evaluate CD8+ T cell concentrations before and after radiation therapy. The model was validated using data from five patients in an ongoing clinical trial and identifies varying patient-specific immune system response following radiation treatment.

Novel theranostic PET imaging agent for patients with advanced rectal cancer

Presentation time and location: Tuesday, Oct. 1, from 5:15 to 5:25 p.m. ET in Room 152

In an ongoing pilot study, Jeffrey Wong, M.D., City of Hope professor of radiation oncology, and colleagues found that a radioactive molecule attached to a monoclonal antibody (Cu-64-Anti-CEA M5A) shows promise as a theranostic — therapy plus diagnostic — tool that allows experts to identify disease sites in patients with rectal cancer. It also shows promise as a way to assess response to chemotherapy and radiotherapy received before cancer treatment, such as surgery. More research is needed to fully understand this therapeutic’s disease targeting and efficacy capabilities.

The below oral presentations have already been presented.

A promising treatment regimen for prostate cancer patients

Presentation time and location: Sunday, Sept. 29, from 8:30 to 8:40 a.m. ET in Room 207B

Early data from an ongoing phase 2 trial led by Savita Dandapani, M.D., Ph.D., City of Hope associate professor of radiation oncology, suggests that a promising treatment regimen for patients with metastatic castration-sensitive prostate cancer is radium 223 dichloride (Ra-223) combined with stereotactic body radiation therapy delivered to tumors that have spread to bone. The treatment plan should include 36 weeks of androgen deprivation therapy combined with the radiation. This is an early trial to show that the use of systemic radiation (radiopharmaceuticals) with stereotactic body radiation treatment may help prevent progression of micrometastases.

A new way to determine the strength of phase 3 cancer clinical trials

Presentation time and location: Sunday, Sept. 29, from 5:05 to 5:15 p.m. ET in Room 207B

A team of researchers led by Yufei Liu, M.D., Ph.D., City of Hope assistant clinical professor of radiation oncology, developed a benchmark to assess the strength of phase 3 clinical trials. They evaluated a database of 332 phase 3 oncology trials and found that targeted therapy trials, trials with progression-free survival as a final endpoint and positive trials tend to have the most robust, reproducible data. More work needs to be done to validate the developed benchmark, which could then be leveraged to design better clinical trials.

Repare Therapeutics Announces Phase 1 Data Highlighting Camonsertib in Combination with Radiotherapy Treatment Presented at the ASTRO Annual Meeting

On September 30, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported data highlighting the clinical benefits of camonsertib, a potential best-in-class oral small molecule ATR inhibitor, combined with palliative radiation for the treatment of metastatic tumors harboring an ataxia-telangiectasia-mutated (ATM) mutation (Press release, Repare Therapeutics, SEP 30, 2024, View Source [SID1234646955]).

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These data from a clinical trial conducted in collaboration with investigators at Memorial-Sloan Kettering Cancer Center were presented at the American Society for Radiation Oncology (ASTRO) annual meeting in Washington, DC by Nancy Lee, MD, FASTRO, Radiation Oncologist & Early Drug Development Specialist, Memorial Sloan Kettering Cancer Center and titled, "Genotypically-Selected Pan Cancer Trial of Camonsertib with Palliative Radiation in the Treatment of Metastatic Tumors Harboring an Ataxia-Telangiectasia Mutated (ATM) Mutation."

"These encouraging early Phase 1 data build further support for the broad clinical potential of camonsertib," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "This first-in-human study combining camonsertib, an ATR inhibitor, with palliative radiation provides early clinical data showing that the combination has the potential to radiosensitize for higher clinical benefit in patients with tumors harboring pathogenic ATM mutations versus those with variants of unknown significance. We are highly encouraged by this early look at the response rate and safety profile of this combination in the Phase 1 setting."

Key Study Findings

Seventeen (17) patients with metastatic tumors harboring ATM mutations were enrolled in the trial; of which 12 had pathogenic ATM mutations and 5 had ATM mutations with variants of unknown significance (VUS).
Primary cancer histology included gastrointestinal (n=5), pancreas (n=5), breast (n=2), lung (n=2), bladder (n=2), and thyroid (n=1).
The recommended phase 2 dose for camonsertib was determined to be 160 mg given once-daily prior to radiation (4Gy) on days 1-5.
Interim response information was available for 16 patients at submission:
At 2-months, there were 2 complete responses (CR), 5 partial responses (PR), and 4 stable disease (SD) in the pathogenic ATM mutation group versus 1 PR and 4 SD in the VUS group.
At 6-months, in 9 evaluable patients, 2 CR, 4 PR, and 1 SD were reported in the pathogenic group versus 1 SD and 1 progressive disease (PD) in the VUS group.

Adicet Bio to Present at the American Society of Gene & Cell Therapy’s (ASGCT) 2024 Advancing Gene + Cell Therapies for Cancer Conference

On September 30, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported acceptance of an oral presentation at the upcoming American Society of Gene & Cell Therapy’s (ASGCT) (Free ASGCT Whitepaper) 2024 Advancing Gene and Cell Therapies for Cancer conference, taking place October 16 – 17, 2024, in Philadelphia, PA (Press release, Adicet Bio, SEP 30, 2024, View Source [SID1234646954]).

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Details of the oral presentation are as follows:

Title: ADI-270: An Armored Allogeneic Anti-CD70 CAR γδ T cell Therapy Designed for Enhanced Potency and Persistence Against Multiple Oncology Indications
Session Name: Novel Targets and Effector Cells
Abstract Number: 8
Presenting Author: Shon Green, Ph.D.
Date and Time: October 17, 2024; 11:15 a.m. – 11:30 a.m. ET