On February 24, 2025 Synnovation Therapeutics, a precision medicine company focused on the discovery and development of best-in-class targeted medicines, reported that the first patient has been dosed in a Phase I trial evaluating SNV4818 as a monotherapy and in combination with fulvestrant, in patients with breast cancer and other solid tumors (Press release, Synnovation Therapeutics, FEB 24, 2025, View Source [SID1234650499]). SNV4818 is a potentially best-in-class pan-mutant-selective PI3Kα inhibitor that may effectively cover kinase (H), helical domain (E), and other PI3Kα mutations clinically. This marks the second Synnovation program to enter the clinic in just over three years since company formation. Synnovation’s lead candidate and potentially best-in-class PARP1 selective program, SNV1521, entered a Phase I trial in January of 2024.

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The SNV4818 Phase I trial, which is being led by Timothy Yap, M.D., Ph.D., Professor of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, is designed to evaluate the safety, tolerability and preliminary efficacy of SNV4818 as a monotherapy in tumor agnostic patients with PI3Kα activating mutations as well as in combination with fulvestrant in HR+/HER2- advanced breast cancer patients.

"We are excited to initiate the clinical development of our second potential best-in-class program, both of which were discovered at Synnovation," said Kevin O’Hayer, M.D., Ph.D., Senior Vice President, Head of Clinical Development at Synnovation. "SNV4818 has the potential to address a significant unmet need for a large population of patients with breast cancer and multiple other tumor types."

The potential of the PI3Kα inhibitor class has been limited by a lack of selectivity against wild type PI3Kα. First generation PI3Kα-isoform specific inhibitors are limited by significant toxicities due to wild type PI3Kα inhibition, including stomatitis, hyperglycemia and rash. A pan-mutant selective, wild-type-sparing, inhibitor enables a wider therapeutic index leading to greater target inhibition which may improve clinical efficacy while decreasing toxicity, unlocking significant potential for this therapeutic class.

SNV4818 is a potentially best-in-class, highly potent pan-mutant PI3Kα inhibitor with excellent selectivity against wild type PI3Kα. This selectivity may allow for broad spectrum PI3Kα mutation coverage including targeting both H1047X and E545/542X classes of driver mutations in breast cancer and other solid tumor indications.

On February 24, 2025 LTZ Therapeutics, an immunotherapy-focused biotech company, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for LTZ-301, a first-in-class myeloid engager immunotherapy intended to treat relapsed or refractory non-Hodgkin lymphoma (r/r NHL) (Press release, LTZ Therapeutics, FEB 24, 2025, View Source [SID1234650498]).

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LTZ-301 is the first asset in the company’s platform to enter clinical trials to determine an initial proof of concept for their myeloid engager approach, to foster immunotherapy. LTZ expects to initiate its Phase 1, open-label, multicenter study in Q2 2025.

"The FDA’s clearance, signaling the initiation of our Phase I study for LTZ-301, represents a significant milestone for the company," said Robert Li, Ph.D., Founder and CEO of LTZ. "We look forward to advancing our lead asset into the clinic to evaluate our myeloid engager approach and its potential as an effective therapy for cancer and other indications, such as autoimmune diseases. Additionally, the recent appointment in October 2024 of Dr. Wayne Godfrey, as LTZ’s Chief Medical Officer, strengthens our company’s scientific and clinical leadership – providing us with great optimism as we move forward in our next phase of clinical development. We’re also delighted to welcome Dr. Alan J. Korman, a globally recognized pioneer in cancer immunology, to LTZ’s scientific advisory board."

LTZ’s approach focuses on the fusion of reverse translational science, with a deep understanding of tumor microenvironment (TME) biology – especially myeloid biology. Macrophages appear to be one of the most prevalent immune cell populations in TME of various hematologic and solid tumors. Therefore, effectively engaging and activating macrophages to kill cancer cells offers significant therapeutic potential for patients. LTZ is developing its own novel Myeloid Engager Platform to primarily enhance the phagocytic function of monocytes and macrophages of different polarization states to foster anti-tumor immunity.

"The company’s preclinical results have demonstrated promising activity and safety, suggesting applicability of LTZ’s platform to treat a variety of cancer indications and autoimmune diseases – where the unmet need is incredibly high," said Dr. Godfrey. "Through our first in-human trial, we aim to advance our understanding of the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of LTZ-301, targeting CD79b-expressing B-cell lymphoma. I’m excited about the potential of LTZ’s innovative scientific approach and the opportunity to work with LTZ’s accomplished scientific team, with the end goal of improving patient outcomes."

About LTZ-301

LTZ-301 is a novel myeloid engager bi-specific antibody that depletes CD79b+ B-cells via enhancing Fc-gamma receptor (FcγR)-independent antibody dependent cellular phagocytosis (ADCP). CD79b is a unique tumor antigen receptor that is highly expressed in B-cell malignancies, including the ones of relapse/resistance to the existing CD19 or CD20-based therapies. LTZ-301 works by redirecting monocytes and macrophages toward CD79b+ B-cells, leading to enhanced phagocytosis and depletion of cancer cells. The initial study of LTZ-301 will be conducted in patients with r/r NHL for whom no standard therapy is available or where standard treatment has failed. Preclinical studies of LTZ-301 demonstrated potent pharmacology in both in vitro and in vivo studies with a favorable safety profile.

On February 24, 2025 Halda Therapeutics, a clinical-stage biotechnology company developing a novel class of cancer therapies called RIPTAC (Regulated Induced Proximity TArgeting Chimeras) therapeutics, reported that the first patient has been dosed in the first-in-human Phase 1/2 clinical trial (NCT06800313) to evaluate the safety and tolerability of HLD-0915 in the treatment of metastatic castration-resistant prostate cancer (mCRPC) (Press release, Halda Therapeutics, FEB 24, 2025, View Source [SID1234650497]).

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"We are very pleased to have initiated the clinical evaluation of HLD-0915 to address the unmet needs of cancer patients with mCRPC," said Christian Schade, President and CEO of Halda Therapeutics. "Initiation of this study marks a significant step in advancing our novel small molecule RIPTAC modality as an important new approach for the treatment of cancer."

The Phase 1/2 open label, multi-center clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of orally administered, single-agent HLD-0915 in mCRPC patients. The study will include an initial Phase 1 dose escalation portion to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion of HLD-0915 as monotherapy and a Phase 2 expansion cohort to further evaluate the efficacy and safety of HLD-0915. The Phase 1/2 clinical study could enroll up to 80 mCRPC patients.

About HLD-0915

HLD-0915 is an innovative bifunctional small molecule therapy designed to selectively target prostate cancer tumors cells by holding together, with defined orientation and purpose, androgen receptor (a tumor-specific intracellular targeting protein) and a protein with essential function (effector protein). The ternary complex drives the formation of new, or neomorphic, protein-protein interactions, abrogating an essential function within cancer cells which results in an antitumor effect. HLD-0915 is designed to drive specific interactions between selected proteins to achieve optimal activity and pharmacology, as demonstrated in Halda’s preclinical studies. In preclinical prostate cancer models, orally delivered HLD-0915 treatment resulted in tumor shrinkage and declines in prostate-specific antigen (PSA), while delivering a favorable therapeutic index including in models of drug resistance.

On February 24, 2025 Healx, an AI-enabled, clinical-stage biotech company dedicated to rare diseases, reported the first patient has been dosed in INSPIRE-NF1, a Phase 2 trial evaluating the safety and efficacy of HLX-1502, an oral investigational therapy, in patients with neurofibromatosis type 1 (NF1) (Press release, Healx, FEB 24, 2025, View Source [SID1234650496]).

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NF1 is a debilitating rare genetic disorder that causes tumours to form along nerves, often manifesting in childhood. It affects approximately one in 2,500 individuals worldwide and can lead to severe complications, including pain, disfigurement, and malignancies. Despite its impact, treatment options remain limited, with many patients facing invasive surgeries or therapies with severe side effects.

A Potential Breakthrough for NF1 Patients

"This trial represents an important step in determining the potential of HLX-1502 as a treatment option for patients," said Simone Manso, head of neurofibromatosis therapy development at Healx. "There are no treatments for many NF1 symptoms; current treatments for NF1 plexiform neurofibromas, such as surgery and MEK inhibitors, are helpful but come with their own set of trade-offs, in terms of lasting complications and side effects. There is a need for new treatments for the NF1 community that balance effectiveness and safety. Evaluating HLX-1502 in this context is a key focus of our research efforts. We are grateful for the support from the Children’s Tumor Foundation, a vital partner in this journey, and to the Neurofibromatosis Clinical Trials Consortium for making this clinical trial a reality."

HLX-1502 was discovered using Healx’s proprietary AI platform, which accelerates the identification of potential drug candidates. The therapy has received Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration, underscoring its potential significance for the NF1 community.

Driving a New Era in NF1 Treatment Innovation

"This is much more than a company milestone—it represents a new hope for the NF1 community," said Tim Guilliams, Ph.D., co-founder and CEO of Healx. "For too long, patients have had limited treatment options that come with serious trade-offs. HLX-1502 is being evaluated as a potential treatment for NF1, with the goal of providing an alternative to existing MEK inhibitors, which have known side effects. If successful, this could mark the beginning of a paradigm shift in NF1 care—one that not only improves patient lives today but also paves the way toward a future where patients no longer have to choose between treatment effectiveness and quality of life."

Partnering for Patient Impact

"We are excited about the launch of this trial and what it could mean for those affected by NF1 worldwide," said Michael Fisher, M.D., director of the NF Program and chief of the Neuro-Oncology Section at the Children’s Hospital of Philadelphia, and the group chair of the NF1 Clinical Trials Consortium. "Our consortium, consisting of 24 clinical centers across the United States and Australia, is committed to pushing NF research forward and finding new therapies for individuals with neurofibromatosis and schwannomatosis. Healx’s innovative approach to treatment discovery gives us renewed hope for continued meaningful progress."

The NF1 Clinical Trials Consortium has an Operations Center based at the University of Alabama at Birmingham (UAB), led by Girish Dhall, M.D., and Karen Cole-Plourde, and a Data Coordinating Center at CHOP led by Richard Aplenc, M.D., Ph.D.

About the INSPIRE-NF1 Study

INSPIRE-NF1 is a Phase 2, open-label, single-arm study evaluating the safety and efficacy of HLX-1502 in NF1 patients with plexiform neurofibromas (PNs). These aggressive tumours can lead to severe complications, including functional impairments and malignant transformation. The trial is enrolling approximately 20 patients in the U.S., focusing on key outcome measures such as tumour response rate, safety and tolerability, and pharmacokinetics. Additional information is available at clinicaltrials.gov (NCT06541847).

About Neurofibromatosis Type 1 (NF1)

NF1 is a rare genetic disorder that predisposes individuals to develop multiple tumours, affecting roughly 3 million people worldwide. Plexiform neurofibromas can cause severe disability, while cutaneous neurofibromas—benign but often numerous tumours—result in significant cosmetic and psychological distress. Treatment options are extremely limited, highlighting an urgent unmet need.

On February 24, 2025 OS Therapies, Inc. (NYSE-A: OSTX), a clinical-stage biotechnology company advancing immunotherapies and targeted drug conjugates for cancer treatment, reported the formation of subsidiary OS Drug Conjugates (OSDC) (Press release, OS Therapies, FEB 24, 2025, View Source [SID1234650495]). The formation of OSDC coincides with formal strategic options initiatives to create value from the Company’s leading-edge, patented silicone dioxide-based, pH sensitive tunable antibody drug conjugates (tADC) & other tunable drug conjugates (tDC) platforms. The Company has initiated discussions with clinical-stage ADC therapeutics companies in the U.S., China and other jurisdictions to form joint ventures (JVs) pairing those companies’ clinical-stage assets with certain assets from the tADC and/or tDC platforms and spinning the JVs into standalone public companies. If successful, OS Therapies intends to provide stock dividends of the public JVs to shareholders.

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The OST-tADC and OST-tDC technologies are centered around the Company’s proprietary next-generation tunable Antibody Drug Conjugate (tADC) and tunable Drug Conjugates (tDC) platforms. These advanced technologies incorporate pH-sensitive silicon-based linkers: SiLinkers to link the targeting antibodies (or antibody fragments) and therapeutic moieties together while coating the entire package with pH sensitive coating. This strategy can release multiple therapeutic agents selectively within the tumor and tumor microenvironment, which have lower pH levels than the rest of the body. This approach aims to maximize the therapeutic effects while minimizing damage to healthy cells.

BCC Research estimates that the global market for antibody-drug conjugates is estimated to increase from $10.8 billion in 2023 to $47.0 billion by 2029, at a compound annual growth rate (CAGR) of 28.4% from 2024 through 2029.