On December 26, 2023 Nectin Therapeutics Ltd., (Nectin), a biotechnology company developing novel targeted immunotherapies that address resistance to approved immune oncology treatments, reported that it has progressed its Phase 1 clinical trial of NTX1088 to include a combination therapy arm with the immune-oncology drug KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, and expanded the trial to four additional global sites to include Sheba Medical Center, Hadassah Medical Center, Ochsner Health, and City of Hope along with flagship site, MD Anderson Cancer Center (Press release, Nectin Therapeutics, DEC 26, 2023, View Source [SID1234638798]).

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NTX1088 is Nectin’s First-in-Class lead candidate – a highly potent monoclonal antibody directed against PVR (CD155), a transmembrane protein expressed on cancer cells and associated with resistance to PD1 and PDL1 immune checkpoint inhibitors. PVR blockade by NTX1088 is the first and only therapeutic approach aimed at restoring the antitumor immune activity of DNAM1 (CD226). DNAM1 is a cell surface glycoprotein, central to the function of T and NK cells, that is degraded by PVR on tumor cells. Restoring the expression and activation of DNAM1 by blocking PVR results in increased antitumor activity from T and NK cells. PVR blockade by NTX1088 further stimulates an antitumor immune response by preventing the suppressing signaling of several immune checkpoint receptors, including TIGIT and CD96. NTX1088 is currently being clinically evaluated as a monotherapy and in combination with KEYTRUDA (pembrolizumab).

"We are very pleased to treat Israeli patients as part of NTX1088’s clinical trial," said Dr. Raanan Berger, Director of the Cancer Center at the Sheba Medical Center. "We are impressed by the pre-clinical data and the novel mechanism of action of PVR blockade and are looking forward to collaborating with Nectin Therapeutics to evaluate the impact of this first-in-class therapy for cancer patients."

"Nectin’s innovative pipeline holds a therapeutic promise for patients with hard-to-treat cancers. This transformational potential is proudly driven by dedicated research efforts in Israel, making it very compelling for Nectin to establish trial sites close to home," said Dr. Keren Paz, Chief Development Officer of Nectin Therapeutics. "We are encouraged by the rapid progress of our NTX1088 clinical program and are excited to expand it globally."

About NTX1088

NTX1088 is a first-in-class monoclonal antibody directed against a key immune checkpoint, PVR (CD155), currently in a Phase I clinical trial. NTX1088 blocks the interaction between PVR and DNAM1(CD226), a transmembrane molecule, involved in the activation of anti-cancer T and NK cells. By preventing internalization and degradation of DNAM1, NTX1088 leads to restoration of DNAM1 expression on the surface of immune cells, resulting in robust antitumor activity. NTX1088 also blocks PVR interactions with its other ligands, such as TIGIT and CD96, preventing their immune inhibitory signaling. NTX1088 demonstrates superior antitumor activity compared to approved and investigational immune checkpoint inhibitors in preclinical models and had a favorable safety profile in non-human primates. NTX1088 is currently being clinically evaluated as a monotherapy and in combination with KEYTRUDA (pembrolizumab).

On December 26, 2023 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the status of its dose escalation/dose expansion Phase 1/2 Study ONCT-808-101, evaluating the company’s ROR1-targeting autologous CAR T cell therapy ONCT-808 for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment (Press release, Oncternal Therapeutics, DEC 26, 2023, View Source [SID1234638797]).

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At the initial dose of 1×106 CAR T cells per kg, two of the three patients achieved complete metabolic response (CMR) and the third achieved a partial response (PR) by FDG PET-CT. Common adverse events in this dosing cohort included decreased blood counts, pneumonia and Grade 1-2 cytokine release syndrome (CRS) as of a 4 December 2023 data cutoff.

The first patient treated at the second dose level of 3×106 CAR T cells per kg, an 80-year-old with bulky disease who had received four previous lines of therapy including CD19 CAR T, experienced a Grade 5 (fatal) serious adverse event consistent with CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). No evidence of his lymphoma was found histologically, based on the patient’s initial autopsy report.

Oncternal has been in communication and is aligned with the Food and Drug Administration (FDA) on our proposed protocol changes that include modified eligibility criteria and testing lower doses of ONCT-808 for future patients in the study.

Salim Yazji M.D., Chief Medical Officer at Oncternal Therapeutics, commented, "The safety of every patient who participates in our studies is of the utmost priority for us. We believe these early disease response data indicate that ONCT-808 is a particularly potent autologous CAR T product with the potential to address significant unmet needs for patients with aggressive B-cell malignancies. With this clear path forward, we plan to implement the protocol amendment as rapidly as possible."

On December 26, 2023 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported that partner LianBio has entered into an agreement with Janssen Pharmaceutica NV ("Janssen"), a Johnson & Johnson company, whereby LianBio has assigned to Janssen LianBio’s exclusive rights to develop and commercialize potential first-in-class radioenhancer NBTXR3 in China, South Korea, Singapore, and Thailand (Press release, Nanobiotix, DEC 26, 2023, View Source [SID1234638796]).

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"Our collaboration strategy for the development and commercialization of NBTXR3 is rooted in a shared commitment to delivering the potential first-in-class radioenhancer to millions of patients around the world," said Laurent Levy, Nanobiotix co-founder and chairman of the executive board. "LianBio has served as an important partner in expanding our clinical development program in Asia, particularly with their support for our ongoing pivotal phase 3 study evaluating NBTXR3 in head and neck cancer. We look forward to continued momentum in our program and moving NBTXR3 toward global registration."

This agreement consolidates global development and commercialization rights of NBTXR3 with Janssen; streamlines the global alliance for co-development and registration of the radioenhancer with Nanobiotix; and includes all previously agreed upon economic terms between Nanobiotix and LianBio, including the Nanobiotix entitlement to receive up to an aggregate $220 million in potential contingent, development and commercialization milestone payments (less $15 million already paid to Nanobiotix by LianBio) along with tiered, low double-digit royalties based on net sales of NBTXR3 in Asian territories.

Following the deal close, LianBio will support the transition of the asset to Janssen for a period no longer than six months.

About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. Its proof-of-concept was achieved in soft tissue sarcomas for which the product received a European CE mark in 2019. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

Radiotherapy-activated NBTXR3 is being evaluated across multiple solid tumor indications as a single agent or in combination with anti-PD-1 immune checkpoint inhibitors, including in NANORAY-312—a global, randomized phase III study in locally advanced head and neck squamous cell cancers. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the phase III study.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a collaboration strategy to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies evaluating NBTXR3 across tumor types and therapeutic combinations. In 2023 Nanobiotix announced a license agreement for the global co-development and commercialization of NBTXR3 with Janssen Pharmaceutica NV.

On December 26, 2023 Bristol Myers Squibb (NYSE: BMY) and RayzeBio, Inc. (NASDAQ: RYZB) reported a definitive merger agreement under which Bristol Myers Squibb will acquire RayzeBio for $62.50 per share in cash, for a total equity value of approximately $4.1 billion, or $3.6 billion net of estimated cash acquired (Press release, Bristol-Myers Squibb, DEC 26, 2023, View Source [SID1234638794]). The transaction was unanimously approved by both the Bristol Myers Squibb and RayzeBio Boards of Directors.

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RayzeBio is a clinical-stage radiopharmaceutical therapeutics ("RPT") company with an innovation-leading position in actinium-based RPTs and a pipeline of potentially first-in-class and best-in-class drug development programs. Current pipeline programs are targeting the treatment of solid tumors, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), small cell lung cancer, hepatocellular carcinoma and other cancers. There remains a high, unmet need for more effective treatments in solid tumors, and RPTs enable a precision approach to patient treatment. RPTs bind to tumor cells and deliver targeted radiation to induce cancer cell death. Actinium-based RPTs offer potential advantages over currently available RPTs since the high potency and short firing range of the alpha-emitter create the possibility for stronger efficacy and more targeted delivery.

"This transaction enhances our increasingly diversified oncology portfolio by bringing a differentiated platform and pipeline, and further strengthens our growth opportunities in the back half of the decade and beyond," said Christopher Boerner, Ph.D., Chief Executive Officer of Bristol Myers Squibb. "Radiopharmaceutical therapeutics are already transforming cancer care, and RayzeBio is at the forefront of pioneering the application of this novel modality. We look forward to supporting and accelerating RayzeBio’s preclinical and clinical programs and advancing its highly innovative radiopharmaceutical platform."

"Acquiring RayzeBio’s differentiated actinium-based radiopharmaceutical platform will establish Bristol Myers Squibb’s presence in one of the most promising and fastest-growing new modalities for the treatment of patients with solid tumors – delivering radioactive payloads to cancer cells in a targeted manner," said Samit Hirawat, M.D., Executive Vice President, Chief Medical Officer, Drug Development of Bristol Myers Squibb. "In addition, RayzeBio’s platform has the potential to be a significant IND engine, generating several therapeutic candidates in the future by leveraging our global drug development capabilities and infrastructure."

Ken Song, M.D., President and CEO of RayzeBio, said, "Despite therapeutic advances in recent years, the need for more effective treatments in solid tumors persists, and radiopharmaceutical therapeutics are positioned to be an important next wave of innovation in oncology therapy. Bristol Myers Squibb’s well-established presence in oncology and deep expertise in developing, commercializing and manufacturing treatments on a global scale makes it the ideal partner for RayzeBio at this important moment in our evolution. I am excited to see what our team achieves as part of Bristol Myers Squibb."

RayzeBio’s portfolio includes:

Lead program RYZ101 (225Ac-DOTATATE), targeting somatostatin receptor 2 (SSTR2), which is over-expressed in GEP-NETs and extensive stage small cell lung cancer (ES-SCLC). A Phase 3 clinical trial is currently enrolling patients to evaluate RYZ101 in patients with SSTR-positive GEP-NETs who have previously been treated with lutetium-177 based somatostatin therapies. RayzeBio previously reported the interim results of the Phase 1b portion of the ACTION-1 clinical trial, suggesting encouraging efficacy and tolerability. A Phase 1b clinical trial is also currently enrolling patients to evaluate RYZ101 as a first-line treatment of ES-SCLC in combination with standard-of-care therapy.
RYZ801, RayzeBio’s novel proprietary peptide targeting glypican-3 (GPC3) for delivery of actinium- based radioactivity for the treatment of hepatocellular carcinoma (HCC). RYZ801 is currently in IND-enabling studies.
Pipeline also includes an asset targeting CA9, which is expressed in renal cell cancer and is currently in IND-enabling studies.
Multiple first-in-class preclinical assets to treat solid tumors.
RayzeBio is completing construction of a state-of-the-art in-house manufacturing facility in Indianapolis, Indiana, and GMP drug production is expected to begin in the first half of 2024.

The transaction is expected to be treated as a business combination and to be dilutive to Bristol Myers Squibb’s non-GAAP diluted earnings per share by approximately $0.13 in 2024. Bristol Myers Squibb expects to finance the acquisition with primarily new debt issuance. Bristol Myers Squibb’s cash flows and strong financial profile enable continued commitment to strong investment-grade credit ratings and investment for growth through business development opportunities and distributions to shareholders through ongoing dividends and share repurchases.

Transaction Terms and Financing

Under the terms of the merger agreement, Bristol Myers Squibb will promptly commence a tender offer to acquire all of the outstanding shares of RayzeBio common stock at a price of $62.50 per share in an all-cash transaction for a total equity value of approximately $4.1 billion, or $3.6 billion net of estimated cash acquired. RayzeBio’s Board of Directors unanimously recommends that RayzeBio’s shareholders tender their shares in the tender offer.

The transaction is expected to close in the first half of 2024, subject to customary closing conditions, including the tender of a majority of the outstanding shares of RayzeBio’s common stock and the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Following the successful closing of the tender offer, Bristol Myers Squibb will acquire all remaining shares of RayzeBio that are not tendered into the tender offer through a second-step merger at the same price of $62.50 per share.

Advisors

BofA Securities, Inc., is serving as financial advisor to Bristol Myers Squibb, and Covington & Burling LLP is serving as legal counsel. Centerview Partners LLC is serving as financial advisor to RayzeBio, and Cooley LLP is serving as legal counsel.

On December 26, 2023 Axcynsis Therapeutics reported that it is presenting at Biotech Showcase 2024 (Press release, Axcynsis Therapeutics, DEC 26, 2023, View Source [SID1234638793]). This year, registered attendees can view Axcynsis Therapeutics’ presentation live and access a recorded version beginning November 27th – SIX weeks before the event. With 24×7 on-demand access, attendees can view recorded presentations at their convenience when scheduling does not allow viewing during the main event week.

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Dr. Bin Zou will be presenting Axcynsis Therapeutics at the Biotech Showcase.

January 8th, 2024, at 2:45 pm Pacific time

Axcynsis Therapeutics is at the forefront of developing cutting-edge Antibody Drug Conjugate (ADC) therapies. It proudly announced its participation in the Biotech Showcase on January 8th, 2024, in San Francisco.

"We are honored to be presenting at the Biotech Showcase. Axcynsis Therapeutics is dedicated to developing the next generation of ADC platforms and drug candidates, and Axcynsis is uniquely positioned to tackle the substantial and urgent unmet needs in cancer therapeutics."

Biotech Showcase, produced by Demy-Colton and EBD Group, is an investor conference focused on driving advances in therapeutic development by providing a sophisticated networking platform for executives and investors that fosters investment and partnership opportunities. The conference takes place each year in San Francisco during one of the industry’s largest gatherings and busiest weeks.

"We are delighted that Axcynsis Therapeutics will be joining us in San Francisco and presenting at Biotech Showcase this year," said Sara Demy, CEO of Demy-Colton. "Biotech Showcase is a prime opportunity for life science entrepreneurs and investors to come together to discover the potential of innovative technologies that will drive the future of drug discovery."