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.

On September 30, 2024, Gritstone bio, Inc. (the "Company") reported interim data from the Phase 2 portion of its randomized, open-label Phase 2/3 study evaluating its personalized cancer vaccine, GRANITE (GRTC901/GRT-R902), in combination with immune checkpoint blockade for patients with front-line metastatic microsatellite stable colorectal cancer ("MSS-CRC") (Press release, Gritstone Bio, SEP 30, 2024, View Source [SID1234646976]).

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Key Findings from Interim Phase 2 Data in MSS-CRC

Data cut as of August 19, 2024

104 patients were randomized 1:1 in the study: 69 patients (39 GRANITE arm, 30 control arm) are included in the treated analysis below. Demographics and clinical characteristics were balanced between arms (stage, sidedness, presence of liver metastases), with the vast majority (80%) of patients having liver metastases in the treated analysis. Thirty-five patients did not advance to study treatment after oxaliplatin, most commonly due to withdrawing consent (n=15), disease progression (n=8), and other reasons (n=12) (12 in GRANITE arm; 23 in control arm).

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Interim data demonstrated an emerging progression-free survival ("PFS") benefit to all GRANITE recipients (study not statistically powered for PFS)

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21% relative risk reduction of progression or death with GRANITE vs. standard of care ("SOC") control in all treated population (HR=0.79 [95% CI, 0.42-1.s])

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33% (13/39) GRANITE and 23% (7/30) of control patients remain on study and free of progression

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Last circulating tumor DNA ("ctDNA") assessment is below the assay limit of quantitation in 12/13 GRANITE and 4/7 control patients

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Clinical benefit was most notable in patients with low disease burden (defined as patients with ctDNA equal to or below the trial population median value at study entry)

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38% relative risk reduction of progression or death with GRANITE vs. SOC control with low ctDNA subgroup (HR=0.62 [95% CI, 0.23-1.70])

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Low baseline ctDNA is a likely prognostic and predictive factor

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Immune data were consistent with clinical activity

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Functional neoantigen-specific T cells were observed in all 16/16 GRANITE patients tested by ELISPOT

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Association of PFS and peak ex vivo ELISPOT responses was apparent, suggesting that ex vivo ELISPOT may be a surrogate for PFS

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GRANITE demonstrated a favorable safety and tolerability profile

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No patients discontinued study treatment due to an adverse event ("AE")

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Common AEs were the mild systemic and local effects associated with any potent vaccine, i.e. transient flu-like illness

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One treatment-related serious AE (fatigue) occurred in the GRANITE arm (patient continued GRANITE treatment without recurrence upon recovery)

The Company plans to review the PFS data with the U.S. Food and Drug Administration in the coming months and agree on next steps to advance GRANITE, including a potential Phase 2 or 3 trial using ctDNA levels as eligibility criteria.

On September 30, 2024 Ichnos Glenmark Innovation (IGI), an alliance between Ichnos Sciences Inc., a global fully integrated clinical-stage biotech company developing multispecifics in oncology, and Glenmark Pharmaceuticals Ltd., reported a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), a part of the National Institutes of Health (NIH) in the United States (Press release, US NCI, SEP 30, 2024, View Source;utm_medium=rss&utm_campaign=igi-announces-crada-with-national-cancer-institute-to-test-proprietary-oral-cbl-b-inhibitor-treatment-in-triple-negative-breast-cancer [SID1234646925]).

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Under the CRADA, IGI and NCI will collaborate on evaluating IGI’s proprietary Cbl/b small molecule, GRC 65327. "GRC 65327 is a best-in-class, novel, selective, orally active, Cbl-b inhibitor that demonstrates good in vitro potency, in vivo efficacy and an acceptable non-clinical toxicity profile," said Nagaraj Gowda, PhD, Vice-President, Head of Small Molecule Research at IGI.

In the research covered by the CRADA, NCI will first characterize and then test GRC 65327 in immune-competent models of triple-negative breast cancer (TNBC) with the intent of generating preclinical data to support a clinical trial in late-stage TNBC at NCI. Stan Lipkowitz, M.D., Ph.D., Chief of Women’s Malignancies Branch, Deputy Director of the Center for Cancer Research at the NCI, and his team will build on their substantial achievements in early Cbl/b research that include initially cloning the gene and having identified Cbl/b’s role as a negative regulator of the adaptive immune system.

"Small molecule inhibitors of Cbl/b may enhance adaptive anti-tumor activity by increased signaling through the costimulatory pathway in T cells and innate immunity via enhanced NK cell activity," said Dr. Lipkowitz. "My group will test the novel Cbl/b inhibitor developed by IGI in in vitro, cell-based, and in vivo mammary cancer models to evaluate its activity as Cbl/b inhibitors and modulators of adaptive and innate immune response to breast cancers."

"We believe in the power of collaboration to drive innovation. Partnering with Dr. Lipkowitz and the NCI to advance our scientific understanding of GRC 65327 is expected to speed its potential development in TNBC, a cancer with few effective treatment options for patients," said Cyril Konto, M.D., President, Executive Director and CEO of IGI. "In addition, the work of Dr. Lipkowitz’s laboratory in late-stage TNBC complements the program IGI has developed to advance GRC 65327 in other solid tumors."

About IGI’s GRC 65327–Casitas B-Lineage Lymphoma b (Cbl/b) Program: Casitas B-lineage lymphoma b (Cbl/b) is an E3 ubiquitin ligase that has been identified as a key inhibitor of T and NK cells activation in the absence of CD28 costimulation, regulate immune cells activity in PD-1, CTLA4 and TIGIT positive cells. As an intracellular master regulator, Cbl/b inhibition may lead to robust immune cell activation in immune-suppressed tumor microenvironment and induce strong single-agent activity. A first-in-human clinical trial in patients with relapsed/refractory solid tumor indications is expected to start in early 2025. IGI plans to present the preclinical data package for GRC 65327 at an upcoming scientific conference.

On September 30, 2024 Cartherics Pty Ltd ("Cartherics" or "Company"), a biotechnology company developing immune cell therapies for the treatment of cancer and other diseases, reported that it has successfully raised well over its target AU$15M in an oversubscribed financing round (Press release, Cartherics, SEP 30, 2024, View Source [SID1234646960]).

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This funding will support the clinical trial for CTH-401, the Company’s lead cell therapy for ovarian cancer, and expand its pipeline to include other diseases.

Cartherics’ Chief Executive Officer, Prof. Alan Trounson AO commented: "The successful capital raising, in times of scant investment support in biotechnology, is welcome and further supports confidence in the company for the delivery of effective therapies in ovarian cancer and other difficult diseases."

CTH-401 is the only natural killer (NK) cell product currently under development that incorporates a chimeric antigen receptor (CAR) that targets the adenocarcinoma specific antigen, TAG-72 – a well-validated tumour marker, widely expressed in a range of solid tumours, including ovarian, gastric, colorectal, prostate and pancreatic cancers.

Cartherics has demonstrated that CTH-401 is very effective in killing ovarian cancer cells in both tissue culture and animal models, with initiation of the first clinical trial planned for next year.

Cartherics’ Chairman, Bob Moses said: "We are eager to start the CTH-401 clinical trial, building on promising preclinical results. This milestone reflects our commitment to innovative ovarian cancer treatments and our investors’ confidence in our vision to improve patient outcomes and drive growth."

On September 29, 2024 IASO Biotherapeutics ("IASO Bio"), a biopharmaceutical company dedicated to discovering, developing, manufacturing and commercializing innovative cell therapy and antibody products, reported a poster presentation of the comparative clinical outcomes of patients from FUMANBA-1 study with relapsed/refractory multiple myeloma (R/R MM) who received the fully human anti-BCMA CAR-T cell therapy Equecabtagene Autoleucel (Eque-cel, Fucaso) under different lymphodepletion regimensat the 2024 International Myeloma Society (IMS) Annual Meeting (Press release, IASO Biotherapeutics, SEP 29, 2024, IASO Bio Presented Comparative Clinical Outcomes on the Optimal Lymphodepletion Prior to Infution of Equecabtagene Autoleucel（FucasoTM）in Patients with Relapsed Refractory Multiple Myeloma at 2024 IMS Annual Meeting [SID1234646909]). Results indicate that a full lymphodepletion dose can significantly improve the depth and duration of remission, prolong progression-free survival, without more treatment-related toxicity in patients.

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Abstract Number：P-094
Abstract Title: The Optimal Lymphodepletion Prior to Eque-cel in Patients with Refractory Relapsed Multiple Myeloma in FUMANBA-1 Study
Presentation Date：September 28, 2024（UTC-3)

The poster presents a post-hoc analysis of the FUMANBA-1 study which enrolled 91 subjects without prior CAR-T treatment to receive Eque-cel. The median follow-up period was 18.07 months. Of the 91 subjects, 33 underwent a lymphodepletion dose adjustment, while the remaining 58 received the standard lymphodepletion dose. Both groups had similar baseline characteristics, including age range, physical fitness scores, tumor staging, high-risk cytogenetic abnormalities, and previous lines of treatment.

The results indicate that, in terms of efficacy, the overall response rate (ORR) and stringent complete remission rate (sCR) for the standard-dose group were 100% and 82.8%, respectively, while the dose-adjusted group had rates of 97% and 78.8% .The standard-dose group also exhibited greater remission depth and better long-term prognosis, with 92.2% of patients maintaining a duration of response (DOR) exceeding one year, compared to 70.6% in the dose-adjusted group. Additionally, the median time to achieve minimal residual disease (MRD) negativity was longer in the dose-adjusted group at 22 days, compared to 15 days in the standard-dose group. The 12-month MRD negativity rate was 90.4% in the standard-dose group, significantly higher than the 63.7% observed in the dose-adjusted group (HR=3.33, P=0.0166). Regarding the 12-month progression-free survival (PFS) rate, the standard-dose group achieved 92.2% with a median PFS not yet reached, while the dose-adjusted group had a 12-month PFS of 73.5% and a median PFS of 30.28 months (HR=3.64, P=0.0032). A similar trend was noted in PFS among patients receiving a 90% dose adjustment.

In terms of safety, no significant differences in the severity and incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. CRS (grades 1-2) occurred in 94.8% of the standard dose group and 93.9% of the dose-adjusted group, with no severe CRS (≥grade 3) in either group. Apart from one grade 2 ICANS case in the adjusted group, no ICANS (≥grade 3) occurred in either group .

Conclusions：lymphodepletion prior to CAR-T cell therapy is essential for achieving optimal CAR-T efficacy. The study further confirms that appropriate lymphodepletion regimen is crucial for effectiveness of eue-cel treatment, significantly improving treatment outcomes and prognosis. When patients can tolerate it, administering the full lymphodepletion doses, when possible, can lead to greater benefits without increasing toxicity.

The principal investigator of this study, Professor Lugui Qiu, from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and Professor Chunrui Li, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, stated: "The lymphodepletion regimen is crucial for CAR-T cell therapy. Data from this study indicate that standardized and sufficient lymphodepletion can lead to a higher quality of remission and more ideal clearance of minimal residual disease without increasing the potential of adverse reactions. These findings provide a scientific basis to ensure the efficacy and safety of CAR-T cell therapy through optimizing regimens of lymphodepletion, which will ultimately lead to longer survival and improved quality of life for patients with R/R MM."

Dr. Yongke Zhang, Chief Scientific Officer of IASO Bio, said: "We are delighted to present new finding from our FUMANBA-1 study. This study demonstrated the critical role of standard lymphodepletion in enhancing treatment outcomes and prognosis for patients.. these findings will contribute significantly to the establishment and optimization of lymphodepletion preconditioning standards in the field of CAR-T cell therapy, Our goal is to drive the standardization of industry practices, ensuring that every patient receiving CAR-T therapy benefits from a more scientific and efficient treatment plan."

About FUMANBA-1 Study

The FUMANBA-1 Study is a Phase Ib/II, single-arm, multicenter study to assess the efficacy and safety of the investigational drug Equecabtagene Autoleucel, a fully human BCMA CAR-T cell therapy, in patients with R/R MM who have received 3 or more lines of treatment.