SynOx Therapeutics announces $75m Series B round to fund Phase 3 trial of potential best-in-class treatment for TGCT

On April 22, 2024 SynOx Therapeutics Limited ("SynOx" or the "Company"), the late-stage clinical biopharmaceutical company, reported the close of a $75m Series B financing (Press release, SynOx Therapeutics, APR 22, 2024, View Source [SID1234642206]). The financing was co-led by Forbion, HealthCap and new investor Bioqube Ventures.

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The proceeds will be used to generate registrational Phase 3 clinical and CMC data for emactuzumab, SynOx’s potentially best-in-class CSF-1(R) inhibiting monoclonal antibody (mAb) for the treatment of Tenosynovial Giant Cell Tumour (TGCT).

TGCT is a type of tumour that affects the soft tissue lining of joints and tendons and is a highly debilitating disease often impacting large, important joints such as the knee, hip and ankle.

TGCT is a chronic disease which often impacts patients throughout their lives. It seriously impacts quality of life by causing significant loss of function of the affected joints, pain, stiffness, and limiting range of motion. While most patients receive surgical intervention, more than 50% of patients with diffuse disease experience tumour recurrence within three years of surgery1..

Emactuzumab is a novel, next-generation CSF-1R mAb with a potentially best-in-class profile. In earlier clinical work in TGCT2. emactuzumab demonstrated substantial clinical activity with an objective response rate (ORR) of 71%, rapid and robust tumour reduction, a long duration of effect, and significant improvements in functional ability. Importantly, these studies also indicated that emactuzumab has good tolerability and a manageable safety profile. SynOx is initiating a Phase 3 trial (TANGENT) to assess the efficacy and safety of emactuzumab in patients with localized and diffuse TGCT.

As part of the Series B financing both Dr Carlo Incerti, M.D., and Jon Edwards, PhD, have joined the Board of Directors. Dr Incerti has more than three decades of experience in the biopharmaceutical industry and brings an extensive track record in global drug development, including from his time at Sanofi Genzyme where he played a leading role in pioneering therapies for rare and genetic diseases. Jon Edwards brings a decade of therapeutic investment expertise and company creation experience, which includes several public listings and multi-billion-dollar acquisitions.

Ray Barlow, Chief Executive Officer of SynOx Therapeutics, said: "This is a transformational time for SynOx. This substantial funding will allow us to generate registrational data for emactuzumab in TGCT. As a highly effective, next-generation therapy with a short treatment cycle, rapid onset and long duration of response, we believe that emactuzumab is differentiated from other agents in development and will provide a much needed and valuable option for patients suffering from this grievous disease."

Dirk Kersten, General Partner at Forbion, commented: "We are pleased to continue to support the SynOx team as it moves emactuzumab through to BLA and MAA submissions in TGCT. As a late-stage company with a clinically de-risked asset, focused on an attractive and underserved market, SynOx is a good example of the type of company Forbion Growth would typically invest in."

Jon Edwards, Bioqube Ventures commented: "We are excited to join the SynOx syndicate and work with this fantastic team and board. We believe this asset has the potential to generate best-in-class data and are excited to help the team develop the product through approval and launch."

Ton Logtenberg, Non-Executive Chair of SynOx Therapeutics, added: "The support of our existing and new investors is validation of SynOx’s strategy and its great potential as a company. I would like to welcome Carlo Incerti and Jon Edwards to the Board of Directors. Their broad experience and knowledge, particularly in driving forward cutting-edge therapies for rare diseases, and executing deals at the highest level, complement the expertise of our existing directors and will be instrumental as we accelerate the late-stage clinical development of emactuzumab."

Sermonix to Host KOL Fireside Chat on Advancements in the Metastatic Breast Cancer Treatment Landscape

On April 22, 2204 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC) harboring ESR1 mutations, reported it will host a virtual KOL fireside chat on Monday, April 22, 2024 from 12:00 PM to 1:00 PM ET, featuring Senthil Damodaran MD, PhD (MD Anderson Cancer Center) and Seth Wander, MD, PhD (Harvard Medical School, Massachusetts General Hospital) to discuss the unmet need and current treatment landscape for metastatic breast cancer (Press release, Sermonix Pharmaceuticals, APR 22, 2024, View Source [SID1234642204]). To register, click here.

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The event will focus on the Company’s ELAINE (Evaluating Lasofoxifene in ESR1 Mutations) studies investigating lasofoxifene in patients with locally advanced or metastatic estrogen receptor-positive/human epidermal growth factor 2-negative (ER+/HER2-) breast cancer expressing an estrogen receptor 1 (ESR1) mutation.

With Phase 2 ELAINE-1 and ELAINE-2 studies both completed and having demonstrated compelling anti-tumor activity against tumors with increasingly prevalent ESR1 mutations, enrollment is currently open for ELAINE-3, a large, randomized, Phase 3 study with clinical trial sites across the United States, Europe, Asia-Pacific, Israel, and Canada.

A live question and answer session will follow the formal presentations.

Cartesian Therapeutics to Present at the ASGCT 27th Annual Meeting

On April 22, 2024 Cartesian Therapeutics, Inc. (NASDAQ:RNAC) (the "Company"), a clinical-stage biotechnology company pioneering mRNA cell therapy for autoimmune diseases, reported that recently reported twelve-month follow-up data from its Phase 2a trial of Descartes-08 in patients with generalized myasthenia gravis will be featured during an oral presentation at the upcoming American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting being held May 7-11, 2024 in Baltimore, MD (Press release, Selecta Biosciences, APR 22, 2024, View Source [SID1234642203]). Descartes-08, the Company’s lead product candidate, is an autologous anti-B cell maturation antigen (BCMA) mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T).

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Details of the presentation are as follows:

Abstract Number: 241
Title: Investigation of mRNA Cell Therapy as a Treatment for Autoimmune Disease in Patients with Myasthenia Gravis
Session Title: Cell Therapy and Cell-Based Gene Therapy Trials
Session Date/Time: Friday May 10, 2024, 1:30-3:15 p.m. E.T.
Presentation Time: 1:45-2:00 p.m. E.T.
Room: Ballroom 1
A copy of the abstract is available through the ASGCT (Free ASGCT Whitepaper) conference website.

Salubris Biotherapeutics Announces $35 Million in Financing and Provides Pipeline Progress Update

On April 22, 2024 Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, reported a new capital infusion of $35 million to fund continued research and development of clinical and pre-clinical programs (Press release, Salubris Biotherapeutics, APR 22, 2024, View Source [SID1234642202]). SalubrisBio also provided progress updates for JK07, the first investigational antibody fusion protein for heart failure, JK08, the first investigational IL15-CTLA4 antibody fusion for solid tumors and JK06, a first-in-class biparatopic antibody-drug conjugate (ADC) targeting a known tumor antigen.

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"We are pleased with the clinical progress across our pipeline of novel, complex biologic therapeutics, positioning us for multiple inflection points over the coming year and into 2025.", said Sam Murphy, Chief Executive Officer of SalubrisBio. "Enrollment of the first patient in our Phase 2 clinical trial of JK07 is an important milestone in our heart failure program. Promising 6-month, Phase 1b data reported last year suggests that JK07 has the potential to improve heart function and long-term outcomes. We look forward to building on these promising findings and potentially delivering a new treatment option that can restore quality of life for heart failure patients."

JK07 Phase 2 Study Design
RENEU-HF (NCT06369298) is a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose trial designed to evaluate the efficacy and safety of JK07 in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The study is expected to enroll 282 subjects who will be randomly assigned (1:1:1) to receive multiple doses of JK07 low dose, JK07 high dose, or placebo. The co-primary endpoints for HFrEF are improvement in ejection fraction, and safety and tolerability, and the primary endpoint for HFpEF is safety and tolerability.

Together, HFrEF and HFpEF affect an estimated 6.2 million Americans[i] and more than 64 million people worldwide[ii]. Heart failure is a chronic condition in which patients experience progressively worsening symptoms and quality of life, hospitalizations and death.

JK08 Phase 1b/2 Study Progress
The ongoing Phase 1b/2, open label, dose escalation and cohort expansion study (NCT05620134) is designed to evaluate the safety and preliminary anti-tumor activity of JK08 in patients with unresectable locally, advanced or metastatic cancer. More than fifty subjects have received JK08 monotherapy in the ongoing dose escalation cohorts, and the first patient has now been dosed in the cohort expansion phase, which will further define the safety and initial efficacy of JK08 in combination with targeted agents including pembrolizumab. SalubrisBio plans to report additional data from this study in the second half of 2024.

"We are encouraged by the early data observed in the ongoing dose escalation portion of the JK08 Phase 1b/2 study and look forward to exploring the clinical benefit of combining JK08 with pembrolizumab in solid tumors," added Murphy.

JK06 CTA Filing
JK06 is positioned to be the first biparatopic ADC targeting a known tumor antigen for which no approved therapies currently exist. Given limited expression and internalization, this antigen is ideally suited for the biparatopic design intended to overcome both limitations, and JK06 has demonstrated low picomolar affinity and robust internalization of the target. It has further demonstrated a highly favorable risk:benefit profile non-clinically and will now be evaluated in a dose-escalation study, including a basket of solid tumors.

About JK07
JK07 is a recombinant fusion protein consisting of a fully human immunoglobulin IgG1 monoclonal antibody and an active polypeptide fragment of the human growth factor neuregulin [NRG-1]. NRG-1 is a clinically validated growth factor that has shown promising activity in heart failure, but also undesirable side effects. Research has shown that NRG-1 induces signaling through interaction with two different receptors – ErbB3 and ErbB4. The ErbB4 pathway appears to be responsible for the regenerative effects in the heart, while the ErbB3 pathway appears primarily responsible for safety and tolerability limitations of recombinant NRG-1. By blocking ErbB3 signaling with an antibody fusion design, JK07 selectively stimulates the ErbB4 pathway with a favorable pharmacokinetic profile, which has the potential to significantly widen the therapeutic window of NRG-1 and yield better clinical effects.

About JK08
JK08 is a recombinant fusion protein consisting of a CTLA-4-specific antibody and an IL-15 fusion domain. The JK08 design builds upon a breadth of clinical studies with CTLA-4 antibodies and recombinant IL-15 molecules, which together portend synergistic effects in an antibody fusion construct. The CTLA-4-specific antibody ipilimumab validated CTLA-4 as a target for cancer therapy, but response rates are limited. Analysis of clinical samples demonstrated that NK cell activity signatures and ADCC biomarkers correlate with ipilimumab responses. Recombinant IL-15 has exhibited potent stimulation of NK cell expansion and enhancement of ADCC in pre-clinical and clinical studies. Through the incorporation of a CTLA-4 antibody and IL-15 into a single molecule, JK08 can channel the potent immune stimulation of IL-15 through the CTLA-4 antibody domain towards depletion of T-regulatory cells and targeted reversal of immunosuppression which may contribute to cancer progression.

Regeneron to Highlight Advances in Genetic Medicine Research at American Society of Gene and Cell Therapy (ASGCT)

On April 22, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that new and updated data across its genetic medicines portfolio will be presented at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) annual conference in Baltimore, Maryland, from May 7 to 11, 2024 (Press release, Regeneron, APR 22, 2024, View Source [SID1234642201]). Data from 10 abstracts, including six oral presentations, provide insight on Regeneron’s approach to overcoming obstacles to clinical implementation of genetic medicines, from pre-dosing to delivery to long-term sustained expression. The company will also present updated data from the Phase 1/2 CHORD trial investigating DB-OTO in children with profound genetic hearing loss due to mutations of the otoferlin gene.

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"Genetic medicine approaches including gene therapy, gene editing and gene silencing hold incredible promise for people with serious, genetically driven diseases, but some common barriers to practical implementation remain, such as delivery to tissues beyond the liver and waning efficacy over time," said Christos Kyratsous, Ph.D., Senior Vice President and Co-Head of Regeneron Genetic Medicines. "Regeneron continues to advance methods to overcome these obstacles through our proprietary delivery approaches utilizing next-generation viral vectors, particularly specific retargeting antibodies and innovative payloads. Our data at ASGCT (Free ASGCT Whitepaper) also details efforts to sustain expression of treatment over time and better modulate immune response via adeno-associated virus delivery."

"We are continuing to dose patients in our clinical trial of DB-OTO gene therapy for profound hearing loss due to otoferlin deficiency and are advancing additional gene therapy programs toward the clinic. The ASGCT (Free ASGCT Whitepaper) presentation will build on promising early results in the first patient," said Aris Baras, M.D., Senior Vice President, Co-Head of Regeneron Genetic Medicines and Head, Regeneron Genetics Center. "These results raise hope and enthusiasm for the field, and we believe that findings from the program will help us unlock paths forward for gene therapies and genetic medicines for more patients and diseases."

Regeneron presentations at ASGCT (Free ASGCT Whitepaper):

Abstract title Abstract Presenting/Lead
Author Presentation
date/time
(ET)
Oral Presentations
Intracochlear Administration of DB-OTO Gene Therapy in Pediatric Patients with Profound Hearing Loss Due to Otoferlin Mutations: The CHORD Phase 1/2 Open-Label Trial 10 Lawrence Lustig, Columbia University Wednesday, May 8, 9:30-9:45AM ET

Antibody-Based AAV Retargeting to Transferrin Receptor Mediates Efficient Blood Brain Barrier Crossing and In Vivo Gene Delivery to the CNS in Mice and Non-Human Primates 118 Kalyani Nambiar Wednesday, May 8, 4:15-4:30PM ET

Targeted Gene Insertion of Vectorized Monoclonal Antibodies in Non-Human Primates Overcomes AAV Genome Silencing in the Liver and Supports High, Sustained In Vivo Expression of Functional Antibodies 197 Rachel Sattler Thursday, May 9, 5:15-5:30pm ET
Retargeting of AAV Using Bispecific Antibodies 218 Sven Moller-Tank Thursday, May 9, 5:15-5:30PM ET
Tissue De-Targeting Abrogates Hepatotoxicity and Complement-Related Thrombotic Complications Associated with High-Dose AAV Gene Therapies 298 Andrew Baik Friday, May 10, 4:15-4:30PM ET
Orthogonal B Cell and Plasma Cell Immunosuppression Strategies Prevent and Suppress High-Titer Antibody Immunity to Enable AAV Vector Re-Dosing 353 Nicholas Giovannone Saturday, May 11, 8:15-8:30AM ET
Poster Presentations
AAV Conjugated to Antibodies Against p75NTR: A New Platform to Deliver Pain Therapeutics to Nociceptive Sensory Neurons 638 Adina Buxbaum Wednesday, May 8, 12:00-7:00PM ET
A Process for Identifying AAV and Transgene Integrations in Mouse and Human Genomes Using Long Read Oxford Nanopore Sequencing 897 Terrence Turner Wednesday, May 8, 12:00-7:00PM ET
DNA Leakage of rAAV Under Freeze/Thaw Stress and Analytical Method Development for Free DNA Characterization 898 Shuai Li Wednesday, May 8, 12:00-7:00PM ET
Identification of Degradation Pathways of rAAV8 to Aid Stable Drug Product Formulation Development 899 Ariel Chen Wednesday, May 8, 12:00-7:00PM ET
Lectures
Engineering CAR-T Cells with Novel Receptor Architectures N/A Philip Gregory Thursday, May 9, 10:55-11:25AM ET

Pressing Challenges in Gene Therapy N/A Jim Wang Saturday, May 11, 8:00-9:45AM ET