On May 6, 2024 Eisbach Bio GmbH ("Eisbach" or the "Company"), a privately-held clinical-stage biotechnology company pioneering cancer medicines leveraging synthetic lethality, reported that United States Food and Drug Administration (FDA) clearance of its investigational new drug (IND) application for EIS-12656, a small molecule inhibiting the chromatin helicase ALC1 (CHD1L) (Press release, Eisbach Bio, MAY 6, 2024, View Source [SID1234642702]). EIS-12656 targets ALC1 through allosteric mechanisms, suppressing the cancer-relevant genome reorganization induced by DNA damage. This leads to ALC1 chromatin trapping and cancer cell killing.

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EIS-12656 impacts tumors deficient in DNA repair pathways. It demonstrated substantial tumor growth inhibition in preclinical models, including in combination with standard-of-care therapies. Its allosteric mechanism of action should afford selectivity compared to related synthetic lethal targets, contributing to the exceptional safety observed in all relevant preclinical models.

"EIS-12656 selectively targets tumors with no apparent effects on normal tissues." said Adrian Schomburg, Ph.D., Founder and CEO of Eisbach. "Our clinical study will also explore combination therapies that were hindered by combinatorial toxicity in the past."

The discovery of EIS-12656 builds on the pioneering research of Eisbach founder Prof. Andreas Ladurner, whose team discovered that PARP effects in cancer cells are reliant on chromatin remodeling by ALC1. Eisbach built upon this knowledge and designed a first-in-class, once-daily small molecule therapy, directly targeting cancer genome reorganization induced by DNA damage at its source – the PARP-activated helicase ALC1.

About the Phase 1/2 Clinical Trial

The open label study of EIS-12656 will evaluate its safety, tolerability and efficacy in patients with genetically-defined advanced solid tumors. Led by Principal Investigator Timothy A. Yap, M.B.B.S., Ph.D., Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, the trial includes dose escalation of EIS-12656 monotherapy, followed by dose expansion modules and evaluation in patients progressing under PARP inhibitor treatment.

On May 6, 2024 Guangzhou-Israel Biotechnology Fund (GIBF) reported that it has invested $10 million in Nectin Therapeutics Ltd (Press release, Nectin Therapeutics, MAY 6, 2024, View Source [SID1234642701]). Nectin is a biotechnology company developing novel targeted immunotherapies that address resistance to approved immune oncology treatments. The funds will be used to continue the development of Nectin’s portfolio of novel immuno-oncology products, including the advancement of Nectin’s ongoing NTX1088 global Phase 1 clinical trial targeting PVR and the preclinical development of its anti-drug conjugate (ADC) portfolio.

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Nectin is a clinical stage biotechnology company devoted to transforming the lives of cancer patients by leveraging unique insights into the nectin pathways to develop the next generation of immune oncology (IO) therapies. The company’s differentiated therapies have the potential to set new standards for efficacy and patient response rates across various difficult-to-treat cancers. Nectin’s technology addresses major escape mechanisms of current IO therapies through a diverse pipeline of novel monoclonal antibodies and antibody-drug-conjugates. It has a world-class scientific and management team with deep experience in oncology drug development and a successful track record in building biotechnology companies and developing innovative therapies. Nectin is a venture-backed, privately held company, funded by aMoon Fund, Peregrine Ventures, IBF, Integra Holdings, Myeloma Investment Fund (MIF), and Cancer Focus Fund.

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 aiming 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 suppressed 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.

PVR is overexpressed in many solid tumors across different cancer indications, including lung, colorectal, liver, ovarian, breast, adrenal, pancreatic, uterine, head and neck, gastric and esophageal cancers. High PVR expression is associated with poor prognosis and with resistance to PD1 and PDL1 blockade, making PVR an attractive target for both monotherapy and in combination with PD1 blockers, as is currently being clinically evaluated in the combination of NTX1088 and KEYTRUDA (pembrolizumab).

"Nectin is working to usher in a new era of innovative immune-mediated cancer medicines and we are excited to back this important mission and team," said Professor Shlomo Noy, Managing Partner and Chief Medical Officer of GIBF. "We have been following the company closely as it continues to make meaningful progress across its portfolio as it develops transformational therapies that can improve the lives of many cancer patients and their treatment outcomes."

"We are grateful for the support from GIBF which reflects the rapid advancement of our anti-PVR clinical program as well as the progress in our development of several ADC candidates," said Fabian Tenenbaum, CEO of Nectin Therapeutics. "With this new investment we are looking forward to completing both the dose-escalation and dose-expansion trials for NTX1088 and continue our IND-enabling activities of our ADC assets. We value GIBF’s commitment to our mission of developing life-saving therapies and look forward to advancing innovative medicines to improve the lives of cancer patients."

On May 6, 2024 AbbVie (NYSE: ABBV) reported that it will participate in the Bank of America Securities Healthcare Conference on Wednesday, May 15, 2024. Robert A. Michael, president and chief operating officer, Scott T. Reents, executive vice president, chief financial officer, Jeffrey R. Stewart, executive vice president, chief commercial officer and Roopal Thakkar, M.D., senior vice president, chief medical officer, global therapeutics, will present at 12:40 p.m. Central time (Press release, AbbVie, MAY 6, 2024, View Source [SID1234642700]).

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A live audio webcast of the presentation will be accessible through AbbVie’s Investor Relations website at investors.abbvie.com. An archived edition of the session will be available later that day.

On May 6, 2024 Vyriad, Inc., a clinical-stage biotechnology company developing the next generation of targeted genetic therapies, reported that its abstract, In Vivo Generation of αCD19-CAR T Cells Using a Novel LV-based Platform Successfully Clears Advanced NALM-6 Tumor without Noticeable Toxicity, has been selected for an oral presentation at the 27th American Society of Gene & Cell Therapy Annual Meeting to be held May 7-11, 2024, in Baltimore, Maryland (Press release, Vyriad, MAY 6, 2024, View Source;cell-therapy-annual-meeting-302137235.html [SID1234642699]). Vyriad’s presentation will discuss progress in developing its highly targeted, efficient, serum-stable and durable lentiviral vector technology to deliver genetic payloads directly and specifically to CD3+ T cells in vivo.

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Presentation Title: In Vivo Generation of αCD19-CAR T Cells Using a Novel LV-based Platform Successfully Clears Advanced NALM-6 Tumor without Noticeable Toxicity

Session Name: CAR T-cell Therapies

Presentation Date/Time: Thursday, May 9, at 5:15 p.m. EST

Presenting Speaker: Karina Krotova, Ph.D., Principal Scientist, Imanis Life Sciences

Full abstracts are available for online viewing via the ASGCT (Free ASGCT Whitepaper) Annual Meeting website at View Source

On May 6, 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 the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI343 as monotherapy for the treatment of claudin18.2-positive advanced gastric/gastro-esophageal junction adenocarcinoma (GC) patients who have progressed after at least 2 lines of prior systematic treatments (Press release, Innovent Biologics, MAY 6, 2024, View Source [SID1234642698]).

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The BTD for IBI343 was based on the data from an ongoing Phase 1 study (NCT05458219), in which favorable safety and tolerability and promising antitumor activity of IBI343 monotherapy in advanced GC patients were observed. The study results will be published at an upcoming medical conference later in 2024.

Innovent is preparing for a registrational Phase 3 multi-regional clinical trial (MRCT) of IBI343 in patients with claudin18.2-positive, HER2-negative GC (G-HOPE-001, NCT06238843) to be initiated soon.

Dr. Hui Zhou, Senior Vice President of Innovent, said, "GC patients tend to progress after second-line systematic therapies with poor prognosis and have only a half year of survival expectancy. They are in urgent need of effective third-line treatment options. We are glad to see the NMPA granted BTD for IBI343 monotherapy based on the PoC clinical results in GC, and we will continue to validate its efficacy and safety in the registrational MRCT trial. Innovent has a comprehensive and robust oncology pipeline, and, particularly in GC, we have PD-1 inhibitor (TYVYT) for first-line GC treatment and anti-angiogenic drug (CYRAMZA) for second-line GC treatment. We will further explore IBI343’s potential in combination therapy as well as in other solid tumors such as pancreatic cancer."

NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of an investigational drug to treat a serious disease or condition when preliminary clinical evidence indicates that the drug has demonstrated substantial improvement over current therapies. The BTD will not only qualify a drug candidate to receive status for rapid review by the CDE, but it will also allow the sponsor to obtain timely advice and communication from the CDE to accelerate the approval and launch to address the unmet clinical need of patients at an accelerated pace. Click here for the published list of drugs that have been granted BTD by NMPA.

About Gastric/ Gastroesophageal Junction Adenocarcinoma

Gastric cancer is one of the most common malignant tumors in the world and is one of the leading causes of cancer-related deaths globally. The 5-year survival rate of patients with metastatic gastric cancer is less than 5%[i]. China and Japan are countries with highest incidence of gastric cancer[ii]. Currently, chemotherapy combination of fluoropyrimidine and platinum and immune checkpoint inhibitor therapy are the standard-of-care treatments for patients with advanced metastatic gastric cancer. However, systemic therapy has limited efficacy in advanced gastric cancer. In particular, the prognosis for patients with third-line or higher gastric cancer is usually poor, with fewer treatment options and shorter survival expectations. The median survival times for these patients is only about 0.5 year[iii].

Claudin, a member of the tight junction molecule family, is a key structural and functional component of epithelial tight junctions. Among them, CLDN18.2 is normally buried in the gastric mucosa, but the development of malignancy leads to disruption of tight junctions and exposure of CLDN18.2 epitopes on the membrane of tumor cells[iv]. CLDN18.2 is expressed in up to 80% of patients with gastric cancer.

About IBI343 (Claudin18.2 ADC)

IBI343 is an antibody-drug conjugate composed of an anti-claudin18.2 antibody, and a cytotoxic drug exatecan. As a topoisomerase I inhibitor, exatecan effectively kills tumor cells by inhibiting DNA synthesis. Binding of IBI343 to claudin18.2-expressing tumor cells results in claudin18.2-dependent internalization of IBI343. Degradation of the cleavable linker will release the drug that causes DNA damage, leading to apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring tumor cells, resulting in a strong "bystander killing effect" of IBI343.