On September 7, 2022 Nuvalent, Inc. ( Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported it will present preliminary dose escalation data from its ongoing ARROS-1 Phase 1/2 clinical trial of NVL-520 for patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumors during an oral plenary session at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium taking place October 26-28, 2022 in Barcelona, Spain (Press release, Nuvalent, SEP 7, 2022, View Source [SID1234619219]). In addition, new preclinical data will be presented in poster sessions for its ALK-selective inhibitor NVL-655 and its recently nominated HER2-selective inhibitor, NVL-330.

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The NVL-520 oral presentation represents the first report of preliminary safety and clinical activity data from the dose-escalation portion of the company’s ongoing Phase 1/2 ARROS-1 study, evaluating NVL-520 in patients with advanced ROS1-positive NSCLC and other solid tumors. NVL-520 has been designed to address the clinical challenges of emergent treatment resistance, off-target central nervous system (CNS) adverse events, and brain metastases that may limit the use of currently available ROS1 kinase inhibitors. The ARROS-1 clinical trial is continuing to enroll patients in the Phase 1 portion of the study.

The NVL-655 poster presentation will describe new preclinical data demonstrating activity of NVL-655 in additional models derived from patients who have progressed on treatment with earlier-generation ALK inhibitors. NVL-655 has previously demonstrated the potential for a best-in-class profile through broad preclinical activity across diverse ALK oncoproteins, single and compound resistance mutations, and tumor types while maintaining strong selectivity for ALK over TRKB and CNS penetrance.

Clinical investigation of NVL-655 is currently ongoing in the Phase 1 portion of the ALKOVE-1 Phase 1/2 study of NVL-655 for patients with advanced ALK-positive NSCLC and other solid tumors. Nuvalent also continues to advance a discovery program for ALK IXDN compound mutations and plans to leverage insights from the ALKOVE-1 clinical trial to guide development candidate selection, which is no longer planned for 2022.

Nuvalent recently selected NVL-330 as the development candidate from its HER2 exon 20 insertion discovery program. Preclinical characterization of NVL-330 as a HER2-selective, brain-penetrant, small molecule inhibitor with activity against HER2 exon 20 insertion mutations will be shared in a poster presentation.

Nuvalent plans to host a conference call and webcast in conjunction with the data presentation on October 28, 2022. Details for the conference call will be provided at a future date, and, once available, presentation and poster information will be archived on the Nuvalent website at www.nuvalent.com.

Details for the presentations are as follows:
Title: Safety and preliminary clinical activity of NVL-520, a highly selective ROS1 inhibitor, in patients with advanced ROS1 fusion-positive solid tumors
Abstract Number: ENA22-0275
Session Topic: Molecular Targeted Agents
Session Title: New Drugs on the Horizon, Plenary Session 6
Session Date and Time: October 28, 2022, 1:00 p.m. – 1:10 p.m. CEST
Presenter: Alexander Drilon, M.D. (Memorial Sloan Kettering Cancer Center, New York, USA)

Title: Preclinical activity of NVL-655 in patient-derived models of ALK cancers, including those with lorlatinib-resistant G1202R/L1196M compound mutation
Abstract Number: ENA22-0105
Session Title: Poster Session, Molecular Targeted Agents 2
Session Date and Time: October 27, 2022, 10:00 a.m. – 5:00 p.m. CEST
Presenter: Anupong Tangpeerachaikul, Ph.D. (Nuvalent, Cambridge, USA)

Title: NVL-330 is a selective, brain-penetrant inhibitor of oncogenic HER2 exon 20 insertion mutations in preclinical models
Abstract Number: ENA22-0150
Session Title: Poster Session, Molecular Targeted Agents 2
Session Date and Time: October 27, 2022, 10:00 a.m. – 5:00 p.m. CEST
Presenter: Kristin L. Andrews, Ph.D. (Nuvalent, Cambridge, USA)

About NVL-520
NVL-520 is a novel brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 study (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.

About NVL-655
NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

About NVL-330
NVL-330 is a novel, selective, brain-penetrant HER2 inhibitor designed to treat patients with HER2 exon 20 insertion-positive tumors, including those with brain metastases, and to minimize adverse events and dose-limiting toxicities related to off-target inhibition of epidermal growth factor receptor ("EGFR" or "ErbB1"), a HER2 family member.

On September 7, 2022 CASI Pharmaceuticals, Inc. ( Nasdaq: CASI), a U.S. biopharmaceutical company focused on developing and commercializing innovative therapeutics and pharmaceutical products, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported the first-patient-in in China Phase 1 dose-escalation and expansion study of BI-1206, a first-in-class fully human monoclonal antibody (mAb) that targets FcγRIIB, in combination with rituximab in patients with relapsed/refractory Non-Hodgkin’s Lymphoma (NHL) (Press release, CASI Pharmaceuticals, SEP 7, 2022, View Source [SID1234619218]). The study design is to assess the safety, tolerability, pharmacology, and clinical activity of BI-1206. The patient was enrolled at Henan Cancer Hospital.

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Wei-Wu He, Ph.D., CASI’s Chairman, and Chief Executive Officer, commented, "We are excited to dose the first patient in the continued evaluation of BI-1206. BI-1206 has previously shown encouraging early signs of efficacy in Phase 1, a tolerable safety profile, and the potential to be used with multiple therapeutic mAbs that rely on ADCC/CDC* for efficacy. This Phase 1 trial in China will generate valuable information and has the potential to provide early evidence of clinical activity in the treatment of relapsed or refractory Non-Hodgkin’s Lymphoma."

Martin Welschof, CEO of BioInvent, said: "The initiation of this Phase I trial in China is an important milestone for BioInvent as it marks the expansion of the clinical program of our lead drug candidate, BI-1206. The clinical results have been very promising, and we are looking forward to generating additional data together with our partner CASI Pharmaceuticals with the aim of improving treatment for patients with NHL and addressing this significant unmet medical need."

About BI-1206 (Anti-FcyRIIB antibody)
The National Medical Products Administration (NMPA) granted BI-1206 Clinical Trial Application (CTA) approval in December 2021. Ethics committee approval from a leading investigational site was granted in January 2022. BI-1206 is currently being investigated outside of China in two Phase 1/2 trials. One is evaluating the BI-1206 combination with rituximab for the treatment of non-Hodgkin lymphoma (NHL), which includes patients with follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL) who have relapsed or are refractory to rituximab. A second Phase 1/2 trial is investigating BI-1206 in combination with anti-PD1 therapy Keytruda (pembrolizumab) in solid tumors. Earlier this year, the U.S. FDA granted Orphan Drug Designation, for BI-1206, for the treatment of follicular lymphoma, the most common form of slow-growing non-Hodgkin lymphoma.

On September 7, 2022 GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, reported the results from phase I study of GFH018 (TGF-β R1 inhibitor) monotherapy (NCT05051241) for treatment of advanced solid tumor will be presented as a poster at the 2022 European Society for Medical Oncology Meeting in Paris on September 12th (Press release, GenFleet Therapeutics, SEP 7, 2022, View Source [SID1234619217]).

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Through an open-label, multicenter study, GFH018 demonstrated a favorable safety/tolerability profile and preliminary efficacy signal among advanced solid tumor patients that failed to respond to prior standard therapies. No dose-limiting toxicities were observed and over 20% patients with different types of cancer achieved stable disease. Two phase II combination studies of GFH018 with PD-1 inhibitor are ongoing with additional data to be presented at medical meetings in the future.

"We are delighted to collaborate with GenFleet in the clinical research of GFH018 as an innovative small-molecule kinase inhibitor designed to specifically target and inhibit TGF-β R1. We are pleased to report the preliminary efficacy signal and good safety/tolerability profile of GFH018 monotherapy and look forward to the further trials in combination studies." said Professor Ye Guo of Shanghai Oriental Hospital.

"It is the first time for GenFleet to present clinical data at ESMO (Free ESMO Whitepaper), which represents a significant milestone in the company’s multi-regional clinical research and global development. We have recently determined the recommended phase II dose and hope to confirm the response of combination therapies in patients with advanced tumors. Moreover, we expect to release more data related to GFH018 in future academic conferences." said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet.

Phase I study of GFH018, a small molecular TGF-β R1 inhibitor, in patients with advanced solid tumor

Poster 437p, Abstract：#1623, Poster Area: Hall 4

This is an open-label, multicenter study comprising of a modified 3 + 3 dose escalation part followed by an expansion part and the starting dose was 5 mg. Eligible patients with advanced solid tumors failed to standard therapies were administrated with GFH018 BID, 14d on/14d off in 28-day cycles. As of Jan. 25, 2022, 39 patients were sequentially enrolled in the dose escalation part. The median lines of prior therapy were≥3. No dose-limiting toxicities were observed, the maximum tolerated dose was not reached, and no patients discontinued the study treatment due to adverse events.

PK of GFH018 was linear and dose-independent with mean half-life in the range of 3.11 hours to 8.30 hours. Of 24 evaluable patients, 5 achieved stable disease. A patient with thymic carcinoma receiving 50 mg achieved a durable stable disease with tumor shrinkage (maximum lesion decreased by 18.4% and has stayed on treatment for 185 days as of the data cut-off date.

About GFH018 and TGF-β R1

Developed by GenFleet Therapeutics, GFH018 is an orally administered TGF-β R1 inhibitor and entered into phase I clinical trial in 2019. Preclinical data showed evidence of GFH018’s good anti-tumor properties against cancer cells in vivo and in vitro. Besides, translational and mechanistic studies confirmed it effectively acts on TGF-β signaling pathway and synergizes with checkpoint inhibitors.

In the microenvironment of advanced solid tumors, TGF-β signaling pathway can promote epithelial mesenchymal transition (EMT) & metastasis, induce the formation of cancer stem cells and their functional maintenance, inhibit anti-tumor immunity, enhance vasculature and fibrosis, and ultimately result in tumor progression. Among patients of hepatocellular carcinoma, glioma, colorectal cancer, lung cancer, pancreatic cancer, urothelial cancer and other solid tumors, high expression of genes related to TGF-β signaling pathway is frequently discovered in their blood and tumor tissues. The expression level is positively correlated to the malignancy & poor differentiation of tumor and unfavorable prognosis in patients.

On September 7, 2022 Cipla Limited (BSE: 500087) (NSE: CIPLA EQ) ("Cipla") reported that it has received final approval for its Abbreviated New Drug Application (ANDA) for Lenalidomide Capsule 5 mg, 10 mg, 15 mg and 25 mg from the United States Food and Drug Administration (US FDA) (Press release, Cipla, SEP 7, 2022, View Source [SID1234619216]).

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Cipla’s Lenalidomide Capsules are the AB-rated therapeutic equivalent generic version of Bristol Myers Squibb’s (Celgene) Revlimid (Lenalidomide) Capsules.

Lenalidomide is an immunomodulatory prescription drug which is indicated for several hematological malignancies in adults such as; Multiple Myeloma, Myelodysplastic syndromes, Mantle cell lymphoma, Follicular lymphoma, and Marginal Zone lymphoma. Depending on the type of cancer, it can be used as monotherapy or combination as a part of first line regimen, maintenance regimen or relapsed settings.

Lenalidomide capsules are not to be used by pregnant women. It is not known if lenalidomide is safe and effective for children. Lenalidomide Capsules should not be used to treat people with chronic lymphocytic leukemia (CLL) outside of a controlled clinical trial.

According to IQVIA (IMS Health), Revlimid (Lenalidomide) Capsules had US sales of approximately $ 2.58 billion for the 12-month period ending June 2022.

The product will be available for shipping soon.

On September 7, 2022 OncoResponse, a clinical-stage biotech company advancing immunotherapies derived from the immune systems of elite cancer responders, reported a clinical supply agreement with Regeneron for PD-1 inhibitor Libtayo (cemiplimab) (Press release, OncoResponse, SEP 7, 2022, View Source [SID1234619215]). The supply agreement will support the evaluation of Libtayo in combination with OR2805, a fully human monoclonal antibody identified from an elite cancer responder using OncoResponse’s proprietary B-cell discovery platform.

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"We believe the ability of OR2805 to potently activate myeloid cells within the tumor microenvironment will not only provide benefit as a monotherapy, but also improve responses to currently available checkpoint inhibitor immunotherapies such as Libtayo," said Bob Lechleider, MD, Chief Medical Officer of OncoResponse. "We look forward to evaluating the combination of OR2805 with Libtayo, which has demonstrated efficacy in pivotal trials, serving as the basis for FDA approval in three types of advanced cancers. We believe that this combination treatment approach has the potential to improve the outcomes of patients with cancer."

OR2805 is being evaluated in an ongoing Phase 1 study examining safety, pharmacokinetics and preliminary anti-cancer activity in patients with advanced solid tumors alone and in combination with anti-PD-1 therapy. The trial includes a dose escalation phase, followed by several expansion cohorts. The role of potential biomarkers will be evaluated throughout the study, and more intensively in a separate biology cohort. ClinicalTrials.gov identifier: NCT05094804

About OR2805

OR2805 is a fully human antibody discovered using B cells derived from an elite responder to checkpoint inhibitor (CPI) therapy. This antibody binds to CD163 which is highly expressed on tumor associated macrophages (TAMs) that create an immunosuppressive tumor microenvironment and inhibit anti-tumor T-cell responses. High frequency of CD163-expressing TAMs generally predicts an unfavorable prognosis in solid tumors. OR2805 is designed to improve anti-tumor T-cell responses, by reversing the immunosuppression of TAMs, as a therapeutic strategy for monotherapy and in combination with CPI.