On November 13, 2024 Daiichi Sankyo (TSE: 4568) reported that it will highlight new clinical research and real-world data from seven abstracts for TURALIO (pexidartinib) at the Connective Tissue Oncology Society (#CTOS2024) 2024 Annual Meeting (Press release, Daiichi Sankyo, NOV 13, 2024, https://www.businesswire.com/news/home/20241113520939/en/Daiichi-Sankyo-to-Showcase-TURALIO%C2%AE-Research-in-Patients-with-Tenosynovial-Giant-Cell-Tumor-at-CTOS [SID1234648313]).

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TURALIO is the first and only oral systemic therapy approved in the U.S. for adult patients with tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. TGCT is a rare and typically non-malignant tumor that affects small and large joints.1,2,3

Data at CTOS will highlight ongoing TURALIO research, including two analyses from the ENLIVEN phase 3 trial. One analysis evaluates the efficacy of TURALIO according to surgical history and the feasibility of surgery following treatment with TURALIO. The other is an exploratory analysis examining the dose of TURALIO at the time of objective response and the first timepoint response of progressive disease in relation to adverse events.

"These latest data being presented at CTOS continue to support the role of TURALIO as a treatment option for certain patients with tenosynovial giant cell tumor," said Dan Switzer, Head of U.S. Oncology Business, Daiichi Sankyo, Inc. "As a leader in TGCT research and development, Daiichi Sankyo has made significant progress in transforming the treatment landscape for patients with this rare, debilitating tumor and we remain committed to educating the medical community on identifying appropriate patients who may be eligible for treatment with TURALIO."

Additional TURALIO data at CTOS include health-related quality of life (HRQOL) outcomes from a phase 4 trial evaluating the discontinuation and re-treatment in patients with TGCT previously treated with TURALIO and a trial-in-progress of a phase 4 trial evaluating the risk of idiosyncratic cholestatic hepatoxicity associated with TURALIO treatment.

Other clinical research includes interim results from an investigator-initiated phase 1 trial evaluating the safety and tolerability of TURALIO in pediatric patients and young adults with TGCT, a case study reporting the use of TURALIO as an upfront treatment strategy for TCGT and results of a real-world assessment evaluating symptom change in patients with TGCT receiving TURALIO.

An overview of TURALIO data to be presented at CTOS includes:

Presentation Title

Author

Presentation (PST)

Pexidartinib use in patients with tenosynovial giant cell tumor: an analysis of the phase 3 randomized ENLIVEN clinical trial according to surgical history

J. Healey

Oral Presentation
Saturday, November 16
3:30 – 4:30 pm

Tumor response and regrowth in relation to clinical events among pexidartinib-treated subjects in the phase 3 ENLIVEN trial

J. Desai

Poster Session
Thursday, November 14
5:45 – 6:45 pm

Health-related quality of life from a phase 4 study to evaluate discontinuation and rechallenge of pexidartinib in patients with tenosynovial giant cell tumor previously treated with pexidartinib

J. Desai

Poster Session
Thursday, November 14
5:45 – 6:45 pm

A long-term phase 4 study to evaluate the risk of hepatotoxicity associated with pexidartinib treatment

A. Singh

Poster Session
Thursday, November 14
5:45 – 6:45 pm

Tenosynovial giant cell tumor in children: interim results from a phase 1 study of TURALIO

J. Lake

Poster Session
Thursday, November 14
5:45 – 6:45 pm

Pexidartinib upfront in a case of tenosynovial giant cell tumor: proof of concept for a treatment paradigm shift

E. Palmerini

Poster Session
Thursday, November 14
5:45 – 6:45 pm

Real-world experience of patients newly initiated on pexidartinib for tenosynovial giant cell tumor

D. Dai

Poster Session
Thursday, November 14
5:45 – 6:45 pm

About TGCT (PVNS/GCT-TS)
TGCT, also referred to as pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS), is a rare, typically non-malignant tumor that can be locally aggressive. TGCT affects the synovium-lined joints, bursae and tendon sheaths, resulting in reduced mobility in the affected joint or limb.1,2,3

While the exact incidence of TGCT is not known, it is estimated that the worldwide incidence of TGCT is 43 patients per million person-years.4,5,6 TGCT is subcategorized into two types: localized, which is more common and accounts for 80% to 90% of cases, and diffuse, which accounts for 10% to 20% of cases.5,6 The current standard of care for TGCT is surgical resection.1,7 However, in patients with recurrent, difficult-to-treat, or the diffuse form of TGCT, the tumor may wrap around bone, tendons, ligaments and other parts of the joint. In these cases, the tumor may be difficult to remove and/or may not be amenable to improvement with surgery. Multiple surgeries for more severe cases can lead to significant joint damage, debilitating functional impairments and reduced quality of life, and amputation may be considered.7,8,9

Recurrence rates for localized TGCT are estimated to be up to 15% following complete resection.3,6,10,11,12 Diffuse TGCT recurrence rates are estimated to be up to 55% following complete resection.3,6,10,13 TGCT affects all age groups with the diffuse type on average occurring most often in people below the age of 40, and the localized type typically occurring in people between 30 and 50 years old.1,4,5,6

About TURALIO
TURALIO (pexidartinib) is an oral small molecule that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium.

TURALIO is approved in the U.S. for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery based on the results of the ENLIVEN trial.

Important Safety Information

Indication
TURALIOⓇ (pexidartinib) is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.

WARNING: HEPATOTOXICITY

TURALIO can cause serious and potentially fatal liver injury. Monitor liver tests prior to initiation of TURALIO and at specified intervals during treatment. Withhold and dose reduce or permanently discontinue TURALIO based on severity of hepatotoxicity. TURALIO is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program.

Contraindications
None

Warnings and Precautions
Hepatotoxicity

Hepatotoxicity with ductopenia and cholestasis occurred in patients treated with TURALIO. Across 768 patients who received TURALIO in clinical trials, there were two irreversible cases of cholestatic liver injury. One patient with advanced cancer and ongoing liver toxicity died and one patient required a liver transplant.
The mechanism of cholestatic hepatotoxicity is unknown and its occurrence cannot be predicted. It is unknown whether liver injury occurs in the absence of increased transaminases.
In ENLIVEN, 3 of 61 (5%) patients who received TURALIO developed signs of serious liver injury, defined as alanine aminotransferase (ALT) or alanine aminotransferase (AST) ≥3 × upper limit of normal (ULN) with total bilirubin ≥2 × ULN. In these patients, peak ALT ranged from 6 to 9 × ULN, peak total bilirubin ranged from 2.5 to 15 × ULN, and alkaline phosphatase (ALP) was ≥2 × ULN. ALT, AST and total bilirubin improved to <2 × ULN in these patients 1 to 7 months after discontinuing TURALIO.
Avoid TURALIO in patients with preexisting increased serum transaminases, total bilirubin, or direct bilirubin (>ULN); or active liver or biliary tract disease, including increased ALP.
Monitor liver tests, including AST, ALT, total bilirubin, direct bilirubin, ALP, and gamma-glutamyl transferase (GGT), prior to initiation of TURALIO, weekly for the first 8 weeks, every 2 weeks for the next month and every 3 months thereafter.
Withhold and dose reduce, or permanently discontinue TURALIO based on the severity of the hepatotoxicity. Rechallenge with a reduced dose of TURALIO may result in a recurrence of increased serum transaminases, bilirubin, or ALP. Monitor liver tests weekly for the first month after rechallenge.
TURALIO REMS

Requirements include: 1) prescribers must be certified by enrolling and completing training, 2) patients must complete and sign an enrollment form for inclusion in a patient registry, and 3) pharmacies must be certified and must dispense only to patients who are authorized (enrolled in the REMS patient registry).
Further information is available at www.TURALIOREMS.com or 1-833-887-2546.
Embryo-fetal toxicity

TURALIO may cause fetal harm when administered to a pregnant woman. Advise patients of reproductive potential of the potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to the initiation of TURALIO.
Advise females of reproductive potential to use an effective nonhormonal method of contraception. TURALIO can render hormonal contraceptives ineffective during treatment with TURALIO and for 1 month after the final dose.
Advise males with female partners of reproductive potential to use effective contraception during treatment with TURALIO and for 1 week after the final dose.
Potential Risks Associated with a High-Fat Meal

Taking TURALIO with a high-fat meal increases pexidartinib concentrations, which may increase the incidence and severity of adverse reactions, including hepatotoxicity.
Instruct patients to take TURALIO with a low-fat meal (approximately 11 to 14 grams of total fat) and to avoid taking TURALIO with a high-fat meal (approximately 55 to 65 grams of total fat).
Adverse Reactions

The most common adverse reactions (>20%) were increased lactate dehydrogenase (92%), increased AST (88%), hair color changes (67%), fatigue (64%), increased ALT (64%), decreased neutrophils (44%), increased cholesterol (44%), increased ALP (39%), decreased lymphocytes (38%), eye edema (30%), decreased hemoglobin (30%), rash (28%), dysgeusia (26%), and decreased phosphate (25%).
Drug Interactions

Hepatotoxic products: Avoid coadministration in patients with increased serum transaminases, total bilirubin, or direct bilirubin (>ULN) or active liver or biliary tract disease.
Moderate or strong CYP3A inhibitors and UGT inhibitors: Concomitant use may increase pexidartinib concentrations. Reduce TURALIO dosage if concomitant use cannot be avoided.
Strong CYP3A inducers: Avoid concomitant use due to decreased pexidartinib concentrations.
Acid-reducing agents: Avoid concomitant use of proton pump inhibitors due to decreased pexidartinib concentrations. Use histamine-2 receptor antagonists or antacids if needed.
CYP3A substrates: Avoid concomitant use where minimal concentration changes may lead to serious therapeutic failure (e.g., hormonal contraceptives) due to decreased concentrations of CYP3A substrates.
Use in Specific Populations

Lactation: Advise not to breastfeed and for at least 1 week after the final dose.
Renal impairment: Reduce the dosage for patients with mild to severe renal impairment.
Hepatic impairment: Reduce the dosage for patients with moderate hepatic impairment. TURALIO has not been studied in patients with severe hepatic impairment.
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc, at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed WARNING, and Medication Guide.

On November 13, 2024 Vergent Bioscience, a clinical-stage biotechnology company developing tumor-targeted imaging agents, reported completion of patient enrollment in the company’s Phase 2, multi-center VISUALIZE trial, evaluating the efficacy and safety of abenacianine for injection (VGT-309) in patients with cancer in the lung. Abenacianine for injection is a novel, investigational tumor-targeted fluorescent imaging agent designed to improve the visibility of difficult-to-find and previously undetected tumors during minimally invasive and robotic-assisted surgical procedures (Press release, Vergent Bioscience, NOV 13, 2024, View Source [SID1234648312]).

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"The VISUALIZE trial will provide additional, valuable insights illuminating the potential of our novel imaging agent to address existing deficits in tumor visualization during lung surgery," said John Santini, Ph.D., president and chief executive officer at Vergent Bioscience. "Completing enrollment in the trial is an exciting milestone that reflects our team’s dedication, as well as the commitment of the VISUALIZE clinical investigators and study participants. We look forward to sharing the results of this study."

Data from previous clinical studies of abenacianine for injection suggest the agent allowed surgeons to see tumor tissue during minimally invasive surgery (MIS), including robotic-assisted surgical procedures, providing "molecular sight" and potentially increasing their confidence in MIS.

For the Phase 2 VISUALIZE trial, investigators at six sites in the United States and Australia enrolled 89 patients with cancer in the lung, all of whom received 0.32mg/kg abenacianine for injection as a short infusion 12 to 36 hours prior to surgery. Following data readout from the VISUALIZE trial, Vergent intends to advance the agent into a Phase 3 study. Assuming positive Phase 3 results, the company will file a new drug application (NDA) for abenacianine for injection for cancer in the lung.

About Lung Cancer Surgery

Approximately 25% of all U.S. lung cancer patients undergo lung cancer surgery, which can be a curative treatment if lung cancer is diagnosed early, and all tumor tissue is removed.1 MIS and robotic-assisted surgery methods are increasingly utilized in lung cancer resection because these approaches are associated with shorter hospital stays, smaller incisions, less blood less, and decreased post-operative complications. While these are important advantages, MIS and robotic-assisted surgery often compromise surgeons’ sight and ability to feel tissue during procedures, making it difficult for them to distinguish tumors from normal tissue and ensure all tumor tissue is removed.

About the VISUALIZE Clinical Trial

The Phase 2, multi-center, open-label VISUALIZE study (NCT06145048) was designed to evaluate the efficacy and safety of abenacianine for injection in patients undergoing surgery for proven or suspected cancer in the lung. Each of the 89 patients in the study received 0.32mg/kg abenacianine for injection 12 to 36 hours prior to surgery. Following an attempt to identify each tumor using standard surgical techniques, investigators used a commercially available near-infrared (NIR) endoscope to assess the presence of tumor tissue, which was then confirmed by pathology. Primary efficacy endpoints included visualization of tumors intraoperatively, surgical margin assessment, and identification of additional cancers or positive lymph nodes that may not have been seen preoperatively.

About Abenacianine for Injection (VGT-309)

Abenacianine for injection is a tumor-targeted fluorescent imaging agent designed to enable a complete solution for optimal tumor visualization during open, minimally invasive and robotic-assisted surgical procedures. Abenacianine for injection is delivered to patients via a short intravenous infusion several hours before surgery. Invented in Professor Matt Bogyo’s Lab at Stanford University School of Medicine, the molecule binds tightly (i.e., covalently) to cathepsins, a family of proteases that are overexpressed across a broad range of solid tumors. This approach, if successful, would provide distinct clinical advantages and position abenacianine for injection as an ideal tumor imaging agent. Abenacianine for injection’s imaging component is the near infrared (NIR) dye indocyanine green (ICG), which is compatible with all commercially available NIR intraoperative imaging systems that support MIS technologies and is a preferred dye to minimize confounding background autofluorescence.

On November 13, 2024 Opna Bio, a clinical-stage biopharmaceutical company focused on the discovery and development of novel oncology therapeutics, reported that two abstracts have been accepted for poster presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting, taking place Dec 7-10, 2024 in San Diego (Press release, Opna Bio, NOV 13, 2024, View Source [SID1234648311]). The presentations will highlight data from Opna’s lead clinical programs, OPN-2853 and OPN-6602.

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The data presentations will include an interim analysis of the ongoing Phase 1 study of OPN-2853, a bromodomain and extra-terminal motif (BET) inhibitor being tested in combination with ruxolitinib, a Janus kinase 1/2 (JAK1/2) inhibitor, in patients with myelofibrosis who are no longer responding to ruxolitinib alone. The study is testing the hypothesis that a continuous daily dosing regimen of oral agents will reduce disease burden. This investigator-initiated study is led by Professor Adam Mead at the University of Oxford through a collaboration with Cancer Research UK (CRUK) and is run through the Cancer Research UK Clinical Trials Unit at the University of Birmingham. As of February 2024, 16 patients have been enrolled at different dose levels. Encouraging levels of spleen reduction, with minimal toxicities and adverse events, have been observed thus far.

A second presentation features preclinical data with OPN-6602, an oral, small molecule inhibitor of the E1A binding protein (EP300) and CREB-binding protein (CBP) currently being tested in a Phase 1 trial in multiple myeloma (MM). In human-derived MM models, OPN-6602 suppresses tumor growth, while downregulating key MM driving genes, with synergistic effects observed in combination with dexamethasone, pomalidomide and mezigdomide.

"We are excited about the upcoming data disclosures at ASH (Free ASH Whitepaper). Both OPN-2853 and OPN-6602 were intentionally designed to have a high C-max and short half-life. This distinct pharmacokinetic profile allows for continuous daily dosing that potentially results in a lower incidence of toxicities and improved efficacy," said Gideon Bollag, PhD, chief scientific officer of Opna Bio.

Investigator-sponsored study
Title: "PROMise Trial: Interim analysis of PROMise, a clinical study combining the BET inhibitor OPN-2853 with ruxolitinib in patients with advanced myelofibrosis experiencing an inadequate response to ruxolitinib"
Publication Number: 3186
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster II
Date and Time: December 8th, 6-8 PM
Presenter: Adam Mead, PhD, Professor of Haematology, Radcliffe Department of Medicine, CRUK Senior Cancer Research Fellow

Opna-sponsored research
Title: "OPN-6602, an Orally Bioavailable EP300/CBP Bromodomain Inhibitor, Targets Multiple Myeloma Through Suppression of IRF4 and MYC"
Publication Number: 1908
Session Name: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster I
Date and Time: December 7th, 5:30 – 7:30 PM
Presenter: Bernice Matusow, MS, Director, Preclinical Development, Opna Bio

On November 13, 2024 Zai Lab Limited ("Zai Lab" or the "Company") (NASDAQ: ZLAB; HKEX: 9688), an innovative, commercial-stage biopharmaceutical company, reported that it has commenced an underwritten public offering of $200.0 million of American depositary shares ("ADSs"), each representing ten ordinary shares of the Company with a par value of $0.000006 per share (Press release, Zai Laboratory, NOV 13, 2024, View Source [SID1234648310]). All ADSs will be offered by Zai Lab. Zai Lab expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the ADSs sold in the public offering at the public offering price less underwriting discounts and commissions. Zai Lab intends to use the net proceeds from this offering for general corporate purposes.

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Goldman Sachs (Asia) L.L.C., Jefferies and Leerink Partners are acting as joint book-running managers for the offering. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed.

The offering will be made pursuant to a shelf registration statement on Form S-3ASR, which became automatically effective upon filing with the U.S. Securities and Exchange Commission ("SEC") on April 19, 2024. A preliminary prospectus supplement related to the proposed ADS offering is being filed with the SEC.

Copies of the registration statement on Form S-3ASR, the preliminary prospectus supplement and the accompanying prospectus may be obtained from: (i) Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY, facsimile: 212-902-9316 or by emailing [email protected], (ii) Jefferies LLC, c/o Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected] and (iii) Leerink Partners LLC, c/o Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy ADSs or any other securities, nor shall there be any sale of ADSs in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 13, 2024 Continuity Biosciences, LLC, a new bioscience company dedicated to developing and commercializing cutting-edge technologies for cell reprogramming, immune modulation, and drug delivery, reported its official launch (Press release, Continuity Biosciences, NOV 13, 2024, View Source [SID1234648309]). The company seeks to bridge biopharmaceutical and medical technologies, establishing a new standard for patient-focused treatments for chronic and complex diseases.

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Founded by a team of experienced scientists and industry leaders, Continuity Biosciences aims to enhance emerging therapies, such as cell therapy, by fully leveraging delivery technology. The team includes Bob Whitehead (Executive Chairman), a veteran in the bioscience field known for successful strategic exits and initiatives; Ramakrishna Venugopalan, PhD (Co-Founder & CEO), a former senior executive at AbbVie with expertise in drug delivery for products like Skyrizi and Vyalev; and Alessandro Grattoni, PhD (Chief Scientific Advisor), Chair and Professor of the Department of Nanomedicine at Houston Methodist Hospital and a leader in advanced drug delivery.

"We are thrilled to have licensed several technology platforms from Houston Methodist Hospital and to introduce Continuity Biosciences to the biotechnology and investment communities," said Ramakrishna Venugopalan, Co-Founder & CEO. "There is immense potential at the intersection of biopharmaceuticals and medical technologies, especially in creating combination products that enhance novel therapies. We plan to expand our technology portfolio to provide our partners with diverse strategies for delivering their treatments."

Dr. Grattoni’s pioneering research, along with Continuity’s licensed technologies, focuses on developing implantable nanofluidic systems. These technologies facilitate cell reprogramming, molecular sieving, immune modulation, and sustained therapeutic release over ultra-long periods. Supported by significant funding from organizations like the National Institute of Health, Department of Defense, United States Agency for International Development, Juvenile Diabetes Research Foundation (now Breakthrough T1D), ISS National Lab, and key pharmaceutical partners and foundations, these platforms have vast potential for preventing and treating chronic conditions including cancer, autoimmune, metabolic and infectious diseases. They also offer versatile applications for long-acting drug delivery and in vivo cell reprogramming systems suited for advanced cell and gene therapies.