NovalGen presents NVG-111 clinical data in hematological malignancies in an oral session and preclinical data for next-generation AR T cell engager NVG-222 at the 65th American Society of Hematology Annual Meeting

NovalGen presents NVG-111 clinical data in hematological malignancies in an oral session and preclinical data for next-generation AR T cell engager NVG-222 at the 65th American Society of Hematology Annual Meeting

- Patients with R/R CLL and MCL show good objective responses to ROR1-targeting T cell engager NVG-111 in combination and monotherapy settings -

- Autoregulation (AR) platform displays significant protective effects from T cell engager toxicity and will enter the clinic with NVG-222 in 2024 –

London, United Kingdom, December 10th, 2023– NovalGen Ltd (“NovalGen”), a pioneering clinical stage immunology company, shared promising findings from the NVG-111-101, a First in Human, Phase I clinical study (NCT04763083), in an oral presentation at the 65^th American Society of Hematology Annual meeting, in San Diego, USA. The study showcased positive responses in 58% of evaluable patients with relapsed refractory chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL) across both combination and monotherapy regimens, durable to 24 months.

Noteworthy outcomes include a remarkable achievement of MRD4 negativity in peripheral blood, determined by flow cytometry, in 30% of CLL participants. Furthermore, a complete metabolic response (CMR) by Lugano criteria was observed in one of two mantle cell lymphoma participants. Such outcomes are particularly significant in diseases characterized by poor T cell function and are associated with improved progression free survival and overall survival.

Professor Amit Nathwani, Founder and CEO of NovalGen, expressed his enthusiasm for the results, stating, “The manageable safety profile together with encouraging clinical activity provide a strong foundation for ROR1 targeting T cells engagers and paves the way for their use in other hard to treat malignancies. including solid tumors.”

Dr Jasani the Chief Investigator for this study stated: “Our pilot study shows the potential of ROR1 targeting T cell engagers in participants with CLL and MCL who have failed multiple lines of therapy including stem cell transplantation.”

In addition to presenting these encouraging clinical outcomes, NovalGen is also introducing their proprietary Autoregulation (AR) technology platform. This innovative platform is showcased in the development of NVG-222, a next-generation T cell engager targeting ROR1 but can be applied to a range of immunotherapies including CAR-T cells to improve the therapeutic index.

NVG-222 stands out with its extended half-life, enabling dosing once every two weeks. The enhanced safety profile of this novel molecule allows for higher, more efficacious dosing, potentially leading to improved patient outcomes. Professor Nathwani remarked, "By maintaining the potency of NVG-111 while extending half-life and significantly reducing mode-of-action-related toxicity, NVG-222 has the potential to extend the therapeutic window and set a new standard for patient care for ROR1 positive hematologic malignancies as well as solid tumors."

NovalGen believes that Autoregulation (AR) technology represents a transformative step in immunotherapy development, aiming to eliminate or reduce mode-of-action toxicities that limit the full potential of these new class of therapeutics leading to enhanced outcomes for patients. The company remains committed to advancing innovative solutions that address unmet medical needs and improve the lives of those affected by challenging diseases.

Abstracts presented:

1.       Abstract Title: Time Limited Exposure to a ROR1 Targeting Bispecific T cell Engager (NVG-111) Leads to Durable Response in Subjects with Relapsed Refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL)

Link to Abstract

Session Title: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: New Inhibitors and Cellular Therapies for Treatment of Relapsed CLL

Session Date: Saturday, December 9, 2023

Presentation Time: 4:00 PM - 5:30 PM PT

Location: Manchester Grand Hyatt San Diego, Grand Hall D

Publication Number: 329

Presenting Author: Dr Parag Jasani

2.       Abstract Title: NVG-222: A First-in-Class Autoregulating Half-Life Extended ROR1xCD3 T Cell Engager Heralding a New Class of Safer Drugs

Link to Abstract

Session Title: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II

Session Date: Sunday, December 10, 2023

Presentation Time: 6:00 PM - 8:00 PM PT

Location: San Diego Convention Center, Halls G-H

Publication Number: 2820

Presenting Author: Dr Vincent Muczynski

About NovalGen

NovalGen is a privately held clinical stage immunology company developing breakthrough immunotherapies, with the aim of creating life-saving novel  treatments for people with immunologically driven diseases. Our Autoregulation (AR) platform can be applied to multiple drug modalities for a wide range of indications in oncology, hematology, inflammation and other areas in the immunology space.

Our dedicated team of experienced scientists, physicians and professionals are passionate about building a pipeline of disruptive and differentiated products tailored to the needs of the patient.

The company’s lead program, NVG-111, is an ROR1-targeting bispecific antibody T-cell engager for the treatment of both hematological malignancies and solid tumors using our breakthrough bispecific antibody technology. Our lead AR programme, NVG-222, builds on the success of NVG-111 and is primed for entry into the clinic in 2024.

About Autoregulation (AR)

AR is NovalGen’s proprietary platform for next-generation therapeutics that has the potential to transform the treatment paradigm across multiple indications. AR therapies harness a response-mediated negative-feedback loop that detects when there is the risk of severe toxicities arising from the drug’s mechanism of action. When this occurs, the drug is deactivated at the site of action to prevent serious side effects. As the risk of toxicity reduces the drug is replenished from circulating active drug and treatment continues. AR enables the potential for therapies to be safely given at higher doses and for longer, widening the therapeutic index and resulting in better outcomes for patients.

About Chronic Lymphocytic Leukemia (CLL)

CLL is the most common form of leukemia in the Western world and is a type of cancer that affects a specific type of white blood cell called B-lymphocytes. These abnormal lymphocytes accumulate in the blood, bone marrow, lymph nodes, spleen and other tissues. Common symptoms of CLL can include fatigue, enlarged lymph nodes, and susceptibility to infections. However, not everyone with CLL will experience these symptoms. Treatment options for CLL can vary and may include watchful waiting, chemotherapy, immunotherapy, targeted therapy, or stem cell transplantation, depending on the individual's specific situation and stage of the disease.

About Mantle Cell Lymphoma (MCL)

MCL is an aggressive but rare cancer that affects white blood cell called B-lymphocytes located in the mantle zone the body's lymphatic system. Typical symptoms include swollen lymph nodes, fatigue, and digestive problems. It can be treated with different therapies, including chemotherapy, targeted drugs, and stem cell transplantation depending on the stage of disease and individual factors.