On November 13, 2023 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, reported that Legend Biotech Ireland Limited, a wholly owned subsidiary of Legend Biotech, has entered into an exclusive, global license agreement (License Agreement) with Novartis Pharma AG for certain Legend Biotech chimeric antigen receptor T-cell (CAR-T) cell therapies targeting DLL3, including its autologous CAR-T cell therapy candidate, LB2102 (NCT05680922) (Press release, Legend Biotech, NOV 13, 2023, View Source [SID1234637584]). The License Agreement grants Novartis the exclusive worldwide rights to develop, manufacture and commercialize these cell therapies, and Novartis may apply its T-Charge platform to their manufacture.

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Legend Biotech is initiating clinical development of LB2102 for the treatment of extensive stage small cell lung cancer and large cell neuroendocrine carcinoma after the U.S. Food and Drug Administration (FDA) cleared its investigational new drug application in 2022. In 2023, the FDA granted the product candidate Orphan Drug Designation, a status conferred to drugs or biologics that are intended to treat, diagnose or prevent rare diseases and conditions.2,3

The Novartis T-Charge platform is a next-generation CAR-T cell therapy manufacturing platform designed to preserve T cell stemness and facilitate CAR-T cell expansion primarily in vivo. The T-Charge platform is designed to reduce the need for extensive culture time outside the body and results in T cells with greater proliferative potential, as well as fewer exhausted T cells.4 LB2102 would be the first application of T-Charge by Novartis to a cell therapy candidate targeting solid tumors.

"We believe LB2102 has an innovative CAR design and armor mechanism that increases its anti-tumor activity. The preclinical evidence shows that an autologous CAR-T could be a differentiated treatment option for patients with small cell lung cancer," said Guowei Fang, Chief Scientific Officer and Head of Business Development of Legend Biotech. "We are excited that a major pharmaceutical company with deep roots in oncology and cell therapy has chosen to further this product candidate in the clinic. We are delighted that a combination of our unique candidate design in LB2102 with the T-Charge platform may potentially offer transformative benefits to small cell lung cancer patients."

Under the License Agreement, Legend Biotech will conduct a Phase 1 clinical trial for LB2102 in the U.S. Novartis will conduct all other development for the licensed products.

Under the terms of the License Agreement, Legend Biotech will receive a $100 million upfront payment and will be eligible to receive up to $1.01 billion in clinical, regulatory and commercial milestone payments and tiered royalties. Closing of the transaction is subject to the parties’ receipt of any necessary consents or approvals, including the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976.

On November 13, 2023 Bayer reported that, following discussions with the U.S. Food and Drug Administration (FDA), it will work with the FDA on a voluntary withdrawal of the Aliqopa (copanlisib) U.S. New Drug Application for adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies (Press release, Bayer, NOV 13, 2023, View Source [SID1234637583]).

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Aliqopa was granted accelerated approval by the FDA in September 2017 based on CHRONOS-1, an open-label, single-arm Phase II study. The FDA required clinical benefit to be confirmed through the CHRONOS-4 study. In the study, the addition of Aliqopa to standard immunochemotherapy regimens did not meet the primary endpoint of progression-free survival benefit versus the standard immunochemotherapy control arm in patients with relapsed follicular lymphoma. Bayer intends to publish the results of CHRONOS-4 in a timely manner.

Bayer is exploring access options for patients currently receiving Aliqopa who have experienced a favorable response to treatment, whose treating physician supports continuing treatment with Aliqopa, and for whom there may be no suitable alternative treatments available. Patients currently being treated with Aliqopa should consult their healthcare provider. No new patients should be prescribed Aliqopa. For questions related to ongoing access, please contact Bayer Medical Communications at 1-888-84-Bayer.

About non-Hodgkin’s lymphoma
Non-Hodgkin’s Lymphoma (NHL) comprises a highly heterogeneous group of chronic diseases with poor prognosis. NHL is the most common hematologic malignancy and the tenth most common cancer worldwide.

About Copanlisib (Aliqopa)
Copanlisib is currently approved in the U.S., China and Taiwan as a monotherapy under the brand name Aliqopa for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.

On November 13, 2023 Medivir AB (Nasdaq Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that clinical data from the ongoing phase 1b/2a study of in fostroxacitabine bralpamide (fostrox) in combination with Lenvima (lenvatinib) in hepatocellular carcinoma (HCC), will be presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, January 18-20, 2024 in San Francisco, USA (Press release, Medivir, NOV 13, 2023, View Source;lenvima-in-hcc-and-shares-positive-response-from-type-d-meeting-with-fda-301985850.html [SID1234637582]).

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The abstract, titled "First safety and efficacy data from phase Ib/IIa study of fostroxacitabine bralpamide (fostrox, MIV-818) in combination with lenvatinib in patients with hepatocellular carcinoma (HCC)" will be presented by Dr. Maria Reig, Director of the Barcelona Clinic Liver Cancer (BCLC) and the Liver Oncology Unit at the Hospital Clinic of Barcelona in Spain. The presentation will include updated safety and independently reviewed efficacy data regarding the clinical benefit of fostrox in combination with Lenvima, a tyrosine kinase inhibitor.

Medivir furthermore announces that interactions with the FDA regarding fostrox’s clinical development plan have intensified with a first Type D meeting with a positive response regarding critical elements of the design for the planned phase 2b study. The finalization of the study design will take place in connection with an upcoming Type C meeting to enable study start in 2024. The goal of the upcoming study, as previously communicated, is to apply for accelerated approval.

– "In this phase 1b/2a study, the fostrox + Lenvima combination has shown a good safety profile and promising tumor control in second-line HCC, and we confidently look forward to presenting these data at ASCO (Free ASCO Whitepaper)-GI. Despite some success with first-line immunotherapy, patients with HCC have a poor prognosis and effective second-line treatment options are lacking. The data from this study, combined with the great medical need, opens the possibility of an accelerated approval path, which is why we are now planning for a pivotal, randomized phase 2b study. The FDA’s response at our Type D meeting was a positive step towards our ambition to give this vulnerable patient group access to fostrox as a new treatment option.", says Pia Baumann, CMO at Medivir.

On November 13, 2023 Intensity Therapeutics, Inc. (Nasdaq: INTS), a late-stage biotechnology company that applies novel engineered chemistry to discover and develop proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported financial results for the third quarter ended September 30, 2023, and provided a corporate update (Press release, Intensity Therapeutics, NOV 13, 2023, View Source [SID1234637581]).

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"Metastatic soft tissue sarcoma continues to plague cancer patients who have poor survival outcomes and insufficient therapeutic options. The positive overall survival and disease control rate data from our Phase 1/2 clinical trial of INT230-6 positions our lead candidate as a potential much needed reprieve, keeping the drug inside the tumor while sparing the body of toxicity. We expect to file an IND for a Phase 3 study of INT230-6 in soft tissue sarcoma by the end of 2023 and look forward to progressing this study," said Lewis H. Bender, President and Chief Executive Officer of Intensity.

Mr. Bender added: "To continue the momentum built from our successful upsized IPO in July, we also look forward to reporting additional results from our Phase 2 INVINCIBLE study in presurgical breast cancer at a medical meeting and finalizing the study design and protocol for a Phase 2/3 program in presurgical breast cancer before year end. I am pleased with our pace of progress to advance the clinical development of INT230-6 and am strongly encouraged by data to date, which reinforces the potential of INT230-6 to shift the treatment paradigm of cancer."

Recent Company Highlights

Presented Positive INT230-6 Data in Patients with Refractory Soft Tissue Sarcoma at the Connective Tissue Oncology Society (CTOS). In November, the Company presented positive data from its ongoing Phase 1/2 clinical trial of INT230-6 at the CTOS annual meeting. The data presented demonstrated a strong disease control rate of 93% for subjects in the monotherapy arm while also extending survival in subjects by nearly 15 months when compared to a synthetic control group. INT230-6 was found to be generally safe and well tolerated with the majority of treatment-emergent adverse events being grade 1 or 2.
Received Orphan Drug Designation for Components of INT230-6 for the Treatment of Soft Tissue Sarcoma. In September, Intensity was granted orphan drug designation (ODD) by the US Food and Drug Administration for three active moieties comprising its lead candidate INT230-6: cisplatin, vinblastine sulfate, and the diffusion enhancer SHAO-FA (8-((2-hydroxybenzoyl) amino)octanoate).
Completed Upsized Initial Public Offering (IPO) with Full Exercise of the Over-Allotment Option. In July, Intensity announced that it had closed its IPO with the full exercise of its over-allotment option. Intensity received a total of $20.2 million in net proceeds from the transaction, providing sufficient cash and cash equivalents to fund operations into the second half of 2025.
Anticipated Near-Term Milestones

Report additional results from the Phase 2 INVINCIBLE study in presurgical breast cancer at a medical meeting in 4Q 2023
File an Investigational New Drug (IND) application for a Phase 3 study of INT230-6 in soft tissue sarcoma in 4Q 2023
Finalize the study design for a Phase 2/3 program in presurgical breast cancer in 4Q 2023
Third Quarter 2023 Financial Highlights

Research and Development (R&D) Expenses were $1.4 million for the three months ended September 30, 2023, as compared to $1.2 million for the same period last year. The increase is due to ongoing Phase 3 IT-03 in sarcoma and phase 2/3 IT-04 in presurgical breast cancer, which will continue to incur planning, multiple regulatory filing, manufacturing, study initiation and trial preparation costs in 2023.

General and Administrative (G&A) Expenses were $1.1 million for the three months ended September 30, 2023, as compared to $0.6 million for the same period in 2022. The increase is primarily due to the costs of operating as a public company. The accounting services and legal costs related to the IPO in 2023 were charged directly to the equity section of the balance sheet as a reduction of additional paid in capital.

Interest Expense for the three months ended September 30, 2023, were $0 as compared to $15,123 for the three months ended September 30, 2022. The decrease is due to the convertible notes and accrued interest being converted to common stock at the time of the IPO.

Net Operating Loss for the third quarter ended September 30, 2023, was $2.3 million as compared to $1.8 million for the three months ended September 30, 2022.

Cash, Cash Equivalents and Marketable Securities as of September 30, 2023, were approximately $15.6 million. The Company expects to have sufficient cash to fund current operations into the second half of 2025.

About INT230-6
INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor resulting in a favorable safety profile. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression that so often occurs with systemic chemotherapy.

On November 13, 2023 Charles River Laboratories International, Inc. (NYSE: CRL) and Aitia, a leader in the application of Causal AI and Digital Twins, reported a strategic agreement that gives Aitia access to Logica, Charles River’s Artificial Intelligence (AI) powered drug solution platform, for the optimized discovery and early development of multiple therapeutic programs for neurodegenerative disease and oncology (Press release, Charles River Laboratories, NOV 13, 2023, View Source [SID1234637580]).

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Under the terms of the agreement, Aitia will deploy Logica across their portfolio of novel drug targets with the aim of creating and advancing drug candidates for neurological indications, including Alzheimer’s, Parkinson’s, and Huntington’s diseases and cancers, including prostate cancer and multiple myeloma. According to the World Health Organization (WHO), Alzheimer’s disease (AD), the most common form of dementia, affects 33 million people globally, while Parkinson’s disease (PD) impacts 8.5 million, and it is estimated that Huntington’s disease (HD) affects approximatively 1 in 10,000 people worldwide. There are currently no known cures for these diseases, and the prevalence of all three diseases rises year-over-year. In the field of oncology, there are approximately 1.4 million new cases of prostate cancer and 160,000 new cases of multiple myeloma reported globally each year. Each cancer presents unique challenges with acquired resistance to novel therapies and corresponding rates of overall survival.

"Unraveling the complex genetic and molecular circuitry of neurodegenerative disorders is critical to the discovery of treatments that significantly slow or reverse these devastating diseases," said Colin Hill, Chief Executive Officer and Co-founder of Aitia. "I do not believe we will get there without the insights from our Digital Twins, which now combined with the advantages of Logica, positions Aitia to rapidly translate our discoveries into novel drug candidates. We are excited to join forces with Charles River, leveraging their decades of industry expertise in research to fuel our R&D efforts."

"Combining Aitia’s Digital Twins with Logica’s next-generation solution stands to transform the discovery and development of novel therapeutics for neurological diseases and oncology," said Professor Julie Frearson, Ph.D., Corporate Senior Vice President and Chief Scientific Officer, Charles River. "The research landscape for Alzheimer’s, Parkinson’s, and Huntington’s has moved slowly in recent years, and we are excited for the impact that this combined AI solution can deliver to patients."

Digital Twins: Increasing Translation Through Data
Additionally, Charles River and Aitia have signed a strategic partnership agreement, focused on the development of a patient-derived xenograft (PDX) Digital Twin to predict the best tumor models for in vivo oncology research. The partnership will combine Charles River’s robust, fully-characterized, disease-relevant PDX data and expertise with Aitia’s industry-leading Digital Twin technology to develop PDX Digital Twins in several cancer types. As part of the partnership, Charles River has made an equity investment in Aitia.

In drug discovery, Digital Twins enable the accurate simulation of gene and protein knockdowns at the individual patient level across patient cohorts to discover and genetically validate novel drug targets. This concept can be applied in a similar way to individual tumor types to design more targeted preclinical studies for oncology research. Digital Twins enable the simulation of disease progression and drug response for existing drug candidates to discover biomarkers to better select existing therapies and effective combination therapies.

The Strength of Logica, an Integrated AI Program
In 2022, Charles River and Valo Health launched Logica, leveraging the AI-powered Valo Opal Computational Platform and Charles River’s leading preclinical expertise, providing clients with transformed drug discovery with a single integrated offering seamlessly translating targets to candidate nomination. Logica is offered as a fully managed, risk-sharing model, with most of the client’s cost tied to success.

"Logica has optimized drug discovery," said Emilio Cordova, Executive Director, Logica. "Combining laboratory infrastructure, expert drug hunters, and large-scale compute capabilities, Logica eliminates whitespace and rapidly delivers results."

Logica utilizes industry-leading predictive models, chemical design, and synthesis capabilities, DNA-encoded libraries, in silico high throughput screening from Valo’s Opal Computational Platform as well as Charles River’s leading capabilities in all aspects of discovery optimization including high throughput screening, medicinal chemistry, ADME, biology, pharmacology, and ultimately safety testing and IND submission, joining together for the first time to create a computation-powered, unified target-to-candidate offering.

Last year, Charles River and Flagship’s Pioneering Medicines announced an agreement to deploy Logica across a portfolio of targets with the aim of creating optimized small molecules that lead to novel therapies for unmet medical needs. More recently, Charles River and Related Sciences announced a multi-program collaboration to apply Logica across several previously undrugged targets.