Large cell neuroendocrine carcinoma

BI 764532 is an investigational T-cell engager that redirects T cells towards cancer cells expressing the DLL3 protein DLL3 antigen was discovered using OBT’s proprietary OGAP® drug discovery platform This is the third Fast Track designation for BI 764532 Oxford, UK, San Jose, Calif., 29 November 2023 – Oxford BioTherapeutics (OBT), a clinical stage oncology company with a pipeline of immuno-oncology and Antibody Drug Conjugate (ADC)-based therapies, today announces that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to BI 764532 for the potential treatment of advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC-Lung) expressing DLL3 whose disease has progressed following at least one prior line of treatment including platinum-based chemotherapy. BI 764532 is an investigational DLL3/CD3 IgG-like T-cell engager for potential treatment of patients with LCNEC-Lung that is being developed by Boehringer Ingelheim. The discovery of BI 764532 (OBT620) was enabled through a successful partnership initiated in 2013, leveraging OBT’s proprietary OGAP® drug discovery platform for identification of the DLL3 antigen and Boehringer Ingelheim’s longstanding expertise in oncology and development of biotherapeutics. As of November 2023, the FDA granted Fast Track designation to BI 764532 for the potential treatment of extensive-stage small cell lung cancer (SCLC) whose disease has progressed following at least two prior lines of treatment including platinum-based chemotherapy, and of advanced or metastatic extrapulmonary neuroendocrine carcinomas (epNEC) whose disease has progressed following at least one prior line of treatment including platinum-based chemotherapy. BI 764532 was also granted Orphan Drug designation by the FDA for the treatment of SCLC, and is currently being investigated in a Phase 2 study, ‘DAREON™-5’ (NCT05882058), in patients with relapsed/refractory extensive-stage SCLC and other relapsed/refractory NEC. Christian Rohlff, Chief Executive Officer of OBT, commented: “We are delighted about the clinical development to help address unmet needs for people living with small cell lung cancer and other neuroendocrine carcinomas. This is an important milestone for our teams and exciting news for the community” FDA’s Fast Track designation is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening diseases and that demonstrate the potential to address unmet medical needs. *** About Oxford BioTherapeutics Oxford BioTherapeutics (OBT) is a clinical stage oncology company with a pipeline of first-in-class immuno-oncology (IO) and antibody-drug conjugate (ADC) based therapies designed to fulfil major unmet patient needs in cancer therapeutics. These include bispecific, Chimeric Antigen Receptor T Cell (CAR-T), Antibody Drug Conjugate (ADC) and Antibody Dependent Cell-mediated Cytotoxicity (ADCC) therapeutics. OBT's first clinical program, OBT076, initiated expansion in a US Clinical Trial in 2021 in patients with advanced or refractory solid tumors, including gastric, bladder, ovarian and lung cancer, where CD205 is overexpressed. Infiltration of tumors by immunosuppressive cells correlates with adverse outcomes (lower progression free and overall survival), suggesting that this process contributes to the progression of several cancers. OBT’s proprietary OGAP® target discovery platform is based on one of the world’s largest proprietary cancer membrane proteomic databases, with data on over 5,000 cancer cell proteins providing unique, highly qualified oncology targets, of which three programs are in clinical development in the US and Europe. OBT's IO discovery process provides unique insights into the cancer-immune cell synapse and has identified several novel IO monoclonal and bispecific antibody candidates for cancer therapies. OBT’s pipeline and development capabilities have been validated through multiple strategic partnerships including with Boehringer Ingelheim, ImmunoGen and our cell therapy research collaboration with Kite Pharma as well as other world leaders in antibody development (such as Amgen, WuXi, Medarex (BMS), Alere (Abbott) and BioWa). OBT has a strong oncology focused management team and board with significant experience in developing IO and antibody-based therapies. For more information on Oxford BioTherapeutics, please visit www.oxfordbiotherapeutics.com/ and follow us on LinkedIn. ContactsInvestors:Dr Christian Rohlff, CEOchristian.r@oxfordbiotherapeutics.com Media:MEDiSTRAVA ConsultingSylvie Berrebi, Sandi Greenwood, Erica HollingsworthE : OBT@medistrava.comT : +44 (0) 203 928 6900

Novartis has entered into an exclusive licence agreement with Legend Biotech for global rights to a selection of CAR-T cell therapies targeting DLL3, with the deal potentially worth over $1bn. Under the terms of the agreement, Novartis will gain exclusive worldwide rights to develop, manufacture and commercialise these cell therapies, which include an autologous CAR-T cell therapy candidate (LB2102) that Legend is taking into early-stage clinical development for extensive stage small cell lung cancer and large cell neuroendocrine carcinoma. The deal also allows Novartis to apply its T-Charge cell therapy platform to the manufacturing process of these therapies, with LB2102 set to be the company's first application of T-Charge to a cell therapy candidate targeting solid tumours. In exchange, Legend will receive a $100m upfront payment from Novartis and will be eligible to receive up to $1.01bn in clinical, regulatory and commercial milestone payments and tiered royalties. “We believe LB2102 has an innovative CAR design and armour mechanism that increases its anti-tumour activity,” said Guowei Fang, chief scientific officer and head of business development at Legend Biotech. “The preclinical evidence shows that an autologous CAR-T could be a differentiated treatment option for patients with small cell lung cancer.” Fang added that the combination of LB2102 with Novartis’ T-Charge platform “may potentially offer transformative benefits to small cell lung cancer patients”. The Novartis/Legend agreement is just one of a series of deals that Novartis has made this year. In July, the company announced its acquisition of DTx Pharma , a preclinical stage biotech focused on developing siRNA therapies for neuroscience indications, in a transaction worth up to $1bn. The merger included DTx’s fatty acid ligand-conjugated oligonucleotide platform as well as its lead preclinical therapy for Charcot-Marie-Tooth disease, a slow-progressing and degenerative disease of the peripheral nervous system. The month prior, the Swiss drugmaker also entered into an agreement to acquire Chinook Therapeutics for approximately $3.5bn, marking a notable expansion of its renal pipeline. The deal granted Novartis access to the US biopharma’s two late-stage candidates in development for immunoglobulin A nephropathy, a rare and progressive kidney disease that mostly affects young adults.

Novartis has struck a licensing deal to advance some of Legend Biotech's experimental CAR T-cell therapies targeting DLL3, including its autologous CAR-T candidate LB2102. As part of the deal announced Monday, Novartis will pay Legend $100 million upfront, and has committed to additional milestone payments of up to $1.01 billion upon the achievement of certain clinical, regulatory and commercial targets.A first-in-human Phase I study of LB2102 began in July for the treatment of extensive-stage small-cell lung cancer (SCLC) or large-cell neuroendocrine carcinoma. "We believe LB2102 has an innovative CAR design and armour mechanism that increases its anti-tumour activity," commented Legend's chief scientific officer Guowei Fang, highlighting preclinical evidence that suggests an autologous CAR-T could offer up a differentiated approach for SCLC patients. The Phase I trial of LB2102 has an estimated enrollment of 41 participants and is expected to read out in 2028.Better proliferative potentialThe new licensing deal grants Novartis exclusive worldwide rights to Legend's DLL3-targeting CAR-T therapies, and allows the Swiss drugmaker to apply its T-Charge platform to their manufacture. The platform is designed to preserve T-cell stemness, or the ability to self-renew and mature, resulting in a product that contains greater proliferative potential and fewer exhausted T-cells. With this technology, the expansion of CAR T-cells occurs primarily in vivo, thus eliminating the need for an extended culture time outside of the body, Novartis says. LB2102 would be the first application of T-Charge by Novartis to a cell therapy candidate targeting solid tumours.Under the agreement, Legend will conduct the Phase I trial for LB2102 in the US, while Novartis takes on all other development for licensed products. Aside from the upfront and potential milestone payments, Legend would also be eligible for tiered royalties on any commercialised products down the road.Novartis is currently developing the CD19-directed CAR-T rapcabtagene autoleucel, also known as YTB323, for lupus nephritis and first-line high-risk large B-cell lymphoma in Phase II, as well as for adult acute lymphoblastic leukaemia in a Phase I trial. The company is also working on PHE885, another T-Charge manufactured CAR-T cell therapy, this time directed against BCMA for patients with relapse/refractory multiple myeloma.