On March 11, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that preclinical data on multiple novel bispecific antibodies as well as antibody-drug-conjugates (ADCs) from its oncology pipeline will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (Press release, Innovent Biologics, MAR 11, 2024, View Source [SID1234641027]). The AACR (Free AACR Whitepaper) meeting will take place April 5-10, 2024, in San Diego, California.

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Late-Breaking Research: Experimental and Molecular Therapeutics 1
Topic: IBI3001: a potentially first-in-class site-specifically conjugated B7-H3/EGFR bispecific ADC for multiple solid tumors
Abstract Number: LB055
Presentation Form: Poster
Presentation Time：Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

Topic: IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, demonstrated potent pre-clinical efficacy in solid tumors
Abstract Number: LB056
Presentation Form: Poster
Presentation Time：Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

Topic: Discovery and preclinical characterization of IBI343, a site-specifically conjugated anti-Claudin18.2 ADC for treating solid tumors
Abstract Number: LB057
Presentation Form: Poster
Presentation Time：Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

Poster Session: Immunology – Single Target and Bispecific Antibodies
Topic: A novel TROP2-targeted immune stimulating antibody conjugate (ISAC) with potent anti-tumoral activity and acceptable safety
Abstract Number: 2718
Presentation Form: Poster
Presentation Time: Monday Apr 8, 2024 1:30 PM – 5:00 PM
Location: Poster Section 6
Poster Board Number: 9
Presenting Author: Dr. Huizhong Xiong

Poster Session: Immunology – Immune Modulation Employing Agonist or Co-Stimulatory Approaches
Topic: Tumor targeted-CD28 bispecific antibody with optimized potency, robust anti-tumoral activity and stringent CD3-dependence
Abstract Number: 5295
Presentation Form: Poster
Presentation Time: Tuesday Apr 9, 2024 1:30 PM – 5:00 PM
Location: Poster Section 3
Poster Board Number: 4
Presenting Author: Dr. Huizhong Xiong

Dr. Kaijie He, Vice President of Innovent, stated: "We aim to tackle drug resistance and enhance treatment outcomes in immunotherapy by developing next-generation bispecific antibodies, multi-specific antibodies and ADCs candidates. To select targets that can address broad-spectrum of tumor types is one of our main research direction. We are pleased to present preclinical data of innovative molecules at the AACR (Free AACR Whitepaper) and accepted as Late-breaking Researches. We hope to benefit more patients with continuous advances in life science and technology. "

On March 11, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a publication in Blood Cancer Journal entitled ‘Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry (Press release, Autolus, MAR 11, 2024, View Source [SID1234641026]).’

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Diagnosing leukemic T-cell malignancies poses challenges due to their resemblance to reactive T-cells. In the paper published by Pedro Horna of Mayo Clinic in collaboration with Autolus, the authors introduce a unique approach for identifying T-cell neoplasms by flow cytometry1. This method adopts the recently described monoclonal antibodies targeting TRBC1 and TRBC22, 3, to assess for TRBC-restriction as a surrogate of clonality. The strategy mirrors the routine and broadly adopted analysis of kappa and lambda immunoglobulin chain restriction for the identification of B-cell malignancies.

This innovative and simple strategy to detect clonal expansion of T-cells by flow cytometry has the potential to facilitate the development of more comprehensive diagnostic panels that can be seamlessly integrated into existing screening protocols, obviating the need for separate T-cell clonality assessments. Autolus is working with world leading flow cytometry companies, including Beckman Coulter Life Sciences, BD (Becton, Dickinson and Company) and Thermo Fisher Scientific, in order to enable the development and distribution of diagnostic panels based on these unique TRBC1 and TRBC2 antibodies.

Advancements in diagnostic approaches for T-cell malignancies, coupled with the development of TRBC1 and TRBC2-directed CAR T cell therapeutics4, may contribute to the improvement of therapeutic strategies in this area of unmet clinical need.

1. Horna et al, Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry. Blood Cancer J. 14, 34 (2024). | doi: 10.1038/s41408-024-01002-0

2. Maciocia et al, Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med 23, 1416–1423 (2017) | doi: 10.1038/nm.4444

3. Ferrari et al, Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies. Nat Commun 15, 1583 (2024) | doi: 10.1038/s41467-024-45854-3

4. Cwynarski et al, First in human study of AUTO4, a TRBC1-Targeting CAR T cell therapy in refractory T cell lymphoma. Hematol Oncol 41, 80–81 (2023) | doi: 10.1002/hon.3163_44

On March 11, 2024 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported that Company’s Management will provide a corporate update and participate in one-on-one meetings at the BIO-Europe Spring Conference, to be held in Barcelona, Spain from March 18-20, 2024 (Press release, Theriva Biologics, MAR 11, 2024, View Source [SID1234641024]).

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BIO-Europe Spring Conference
Format: Corporate presentation and one-on-one meetings
Presentation Date: Monday, March 18, 2024
Presentation Time: 3:00pm CET
Presentation Location: Room 133/134, Barcelona International Convention Centre (CCIB)

On March 11, 2024 Sonnet BioTherapeutics Holdings, Inc. ("Sonnet" or the "Company") (NASDAQ:SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported that the first Phase 1b/2a clinical trial of SON-080 was cleared to proceed to Phase 2 after review by the independent DSMB (Press release, Sonnet BioTherapeutics, MAR 11, 2024, View Source [SID1234641023]). This study (SB211, NCT05435742) is being conducted at two sites in Australia in patients with persistent CIPN using a new proprietary version of recombinant human Interleukin-6 (rhIL-6), which required confirmation of safety before continued development in Phase 2. Many drugs cause peripheral nerve damage; patients with CIPN experience discomfort that can result in persistent, unbearable pain that may limit chemotherapeutic treatment.

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SB211 is studying a low dose of rhIL-6 that has an amino acid sequence identical to the native molecule. The trial targets serum levels similar to those induced with moderate exercise, which triggers the natural healing of nerves, muscle, and bone. As a pleiotropic cytokine, native IL-6 participates in several physiological processes, including tissue repair, glucose homeostasis, and the innate immune response at lower levels, but it can result in acute pathological inflammation at higher serum levels. Preclinical models of CIPN and DPN show that low dose rhIL-6 has the potential to stimulate nerve regrowth to re-establish normal sensations, thereby reducing pain and normalizing some of the physiological conditions that had deteriorated due to nerve degeneration. Early versions of rhIL-6, including Serono’s atexakin alfa and others, have been tested in hundreds of patients with cancer, diabetes, idiopathic aplastic anemia, or in healthy controls, showing a maximum tolerated dose of 10 µg/kg three times a week (TIW). However, fever, nausea, and vomiting were prominent at doses over 2 µg/kg TIW. Study SB211 was designed in Phase 1b to show safety using lower doses in CIPN with up to about 1 µg/kg of Sonnet’s new version of IL-6 (SON-080) given subcutaneously TIW for twelve weeks.

The protocol required DSMB to review the unblinded safety and tolerability of SON-080 in the first nine patients in SB211. While the data is still blinded to the rest of the team and we do not have access to the responses by group, the initial safety profile mimics that seen in prior studies with lower doses of exogenous rhIL-6. The most prominent symptoms in SB211 included injection site reactions (redness, bruising, pain, or itching) that resolved within a few days, as well as fatigue, body aches, or nausea that were mostly mild with some symptoms that were moderate. One patient developed severe fatigue and withdrew from the study after one month. All adverse events were transient and reversible. The DSMB concluded that the symptoms were tolerable in the initial patients and the study could proceed to Phase 2. The unblinded safety data from two dose levels of SON-080 compared to placebo are expected during the second half of 2024.

"Completion of the Phase 1b portion of SB211 is an important milestone for Sonnet in the Company’s quest to bring a potentially groundbreaking treatment forward for peripheral neuropathies, where there’s a large unmet need," said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer. "This trial was designed to initially bridge the large atexakin alfa historical safety database in cancer patients and then to study the neuroprotective and neuro-regenerative effects of SON-080 in Phase 2 in a neurotherapy indication. Owing to the larger market opportunity of the DPN indication, we have received greater potential partnering interest in this indication." Dr. Mohan further added, "The inhibition of IL-6 release in diabetic patients, even after moderate exercise, suggests there is tremendous disease modifying potential for the application of rhIL-6 in DPN. Given the high prevalence of neuropathy in diabetes and the commensurate industry interest in this market, we have prioritized DPN as the best potential indication for Phase 2 development. We have initiated a partnering process to move the asset forward towards commercialization."

"Interleukin-6 has been extensively studied in cancer patients in the past, so the use of SON-080 in CIPN was expected to provide a similar adverse event profile at low doses," said Richard Kenney, M.D., Sonnet’s Chief Medical Officer. "The preclinical models showing improvements in nerve function and histology suggest possible benefits in humans with various types of peripheral neuropathy due to cancer and diabetes. This approach is a unique way to actually treat the underlying causes of peripheral neuropathy with rhIL-6, rather than trying to mask the symptoms. Further, given the business priorities, SB211 CIPN development will be placed on hold and the data will be leveraged to initiate a Phase 2 study in the much larger DPN indication."

About the SB211 Phase 1b/2a Trial

The SB211 study is primarily designed to evaluate the safety, PK, PD, and initial efficacy of two dose levels of SON-080 compared to placebo. The drug is self-administered three times a week, subcutaneously, in patients with CIPN lasting at least 3 months after chemotherapy. The study is being conducted at multiple sites in Australia, in a blinded fashion, comparing SON-080 to placebo. The primary endpoint explores the safety and tolerability of SON-080, with key secondary endpoints intended to measure PK, PD, and immunogenicity. Preliminary efficacy is being explored using standardized pain questionnaires over the course of the trial.

On March 11, 2024 Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, reported that it will present two posters with preclinical data highlighting advancements across two distinct modalities at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Ribometrix, MAR 11, 2024, View Source [SID1234641022]).

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The posters will show in vivo anti-tumor efficacy of Ribometrix’s lead candidate targeting the RNA-binding protein eIF4E in combination with standard-of-care across multiple indications, and the Company’s discovery of small molecules that directly bind a complex RNA structure within the c-MYC mRNA in cells, and demonstrate a reduction in c-MYC protein levels.

These new data support the potential for Ribometrix’s RNA-modulating approach to enable drugging well-validated therapeutic targets, including eIF4E and c-MYC, that are currently intractable to traditional small molecule approaches.

Presentation Details:

Abstract Title: Development of novel eIF4E inhibitors to potently and selectively suppress tumor growth across multiple indications

Abstract: 682 / 28
Presenter: Matthew Friedersdorf, Ph.D., Associate Director, Translational Medicine at Ribometrix

Session: PO.ET09.05 – Novel Antitumor Agents 2
Date: Saturday, April 7, 2024

Time: 1:30pm – 5:00pm CT

Abstract Title: Leveraging an RNA-targeting platform for the discovery of cell-active c-MYC mRNA-binding small molecules

Abstract: 680 / 26
Presenter: Katie Warner, SVP of RNA Biology at Ribometrix
Session: PO.ET09.05 – Novel Antitumor Agents 2
Date: Saturday, April 7, 2024

Time: 1:30pm – 5:00pm CT

At the time of presentation, Ribometrix’s posters will be made available on the "Publications" page of the "News" section of its website.

About eIF4E

Eukaryotic translation initiation factor 4E (eIF4E) is a crucial regulatory component of mRNA translation. It selectively promotes pro-oncogenic protein synthesis in response to activation of multiple tumor signaling pathways. Many pro-oncogenic signaling pathways require eIF4E activity to promote tumor growth. Clinically, eIF4E activity is elevated in many kinds of tumor and it is typically associated with poor prognosis. Thus, targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care. Additionally, eIF4E is also central to many resistance mechanisms, therefore eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Ribometrix is developing eIF4E inhibitors as a promising therapeutic strategy to inhibit oncogene expression to enhance efficacy in combination with other therapies and overcome resistance to targeted anti-cancer therapies.

About c-MYC

c-MYC is a well-validated oncogene with broad anti-cancer potential, as c-MYC expression is dysregulated in more than 50% of cancers and a key regulator in nearly every aspect of the oncogenic process. c-MYC has remained intractable to traditional small molecule drug discovery, primarily due to its lack of a defined small molecule binding pocket. By targeting the c-MYC mRNA with small molecules, Ribometrix is bypassing the "undruggable" challenges to successfully reduce c-MYC protein levels and develop a novel anti-cancer therapeutic for c-MYC-driven cancers.