Updated clinical data for NVG-111, a novel ROR1xCD3 bispecific antibody in patients with relapsed / refractory CLL and MCL
Pre-clinical data for a first in class half-life extended T Cell engager targeting ROR-1
NovalGen’s auto-regulation platform expanded into non-oncology indications - in haematology with pre-clinical data for Haemophilia A in an oral presentation

London, United Kingdom, November 3, 2022– NovalGen Ltd (“NovalGen”), a biopharmaceutical company developing breakthrough cancer therapies, alongside an auto-regulation platform, today announces the online publication of three abstracts submitted to the American Society of Hematology Annual meeting, to be held December 10-13, 2022.

“We are delighted to be presenting encouraging additional clinical data in poster presentations from our lead program for patients with relapsed / refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), as well as important pre-clinical data for our first in class half-life extended T Cell engager targeting ROR-1 which demonstrate the inherent value in both our pipeline and our technology base”, said Professor Amit Nathwani, Founder and CEO of NovalGen. “We are still focusing on bispecific antibodies for oncology indications, but we can produce safer existing drugs including a bispecific Factor VIII mimicking antibody with an inbuilt regulating off switch designed to enhance safety without compromising efficacy for Haemophilia A patients, which will be delivered as an oral presentation at the conference.”

Abstracts to be presented:

Abstract Title: First-in-Human Phase I Study of a ROR1 targeting bispecific T cell engager (NVG-111) shows evidence of efficacy in patients with relapsed refractory CLL and MCL (ClinicalTrials.gov identifier: NCT04763083). https://ash.confex.com/ash/2022/webprogram/Paper169658.html

Session Title: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I

Session date and time: Saturday, December 10, 2022
Presentation Time: 5:30 PM - 7:30 PM ET

Session room: Ernest N. Morial Convention Center, Hall D

Publication Number: 1810

Presenting Author: Parag Jasani

As of the July31st, 2022 data cut-off date, 10 patients (8 males and 2 females, median age 60 years) had been enrolled to the study; 3 into single subject ATD cohorts, 3 into 30 μg/day flat dosing cohort (cohort 4) and 4 into cohort 4b that entailed a step-up dosing of NVG-111 in cycle 1 only; (first week cycle1: 3 μg/day, second week, cycle 1: 10 μg/day and week 3, cycle 1: 30μg/day dose). Eight subjects had CLL and 2 MCL. NVG-111 was well tolerated. Adverse events (AEs) were largely limited to week 1 of cycle 1 and all were reversible. The most common AEs were Grade 1 or 2 nausea (70%), headaches (60%), and fatigue (50%) and thrombocytopenia (30%). Grade1/2 cytokine release syndrome (CRS) was observed in (40%) of subjects. Grade 3 dose limiting toxicities occurred in two subjects consisting of immune effector cell–associated neurotoxicity syndrome-like symptoms (ICANS) in one (cohort 4) and ALT and AST elevation (cohort 4b) in the other. Both subjects recovered upon stopping NVG-111. Evidence of T cell activation was observed in all evaluable subjects (9/10). Objective clinical responses were observed in 66% of subjects and included 2 MRD4 negative clinical remissions (CR). These two subjects remained in MRD4 negative CRs at 6 months after completion of treatment. In conclusion, early data shows that NVG-111 is generally well tolerated with a predictable and manageable safety profile. Promising evidence of efficacy was observed which appears to be durable in two subjects with MRD4 negative CR. Dose escalation is ongoing in combination or as monotherapy to determine the maximum tolerated dose/recommended Phase II dose.

Abstract Title: Pre-Clinical Development of a First in Class Half-Life Extended T Cell Engager Targeting ROR-1. https://ash.confex.com/ash/2022/webprogram/Paper168961.html

Session Title: 802. Chemical Biology and Experimental Therapeutics: Poster II

Session date and time: Sunday, December 11, 2022, 6-8pm

Session room: Ernest N. Morial Convention Center, Hall D

Publication Number: 3478

Presenting Author: David Granger

Building on the safety and efficacy data emerging from the Phase I/II trial of NVG-111, NovalGen is looking to develop a half-life extended ROR1xCD3 T cell engager (TCE) with a more convenient once a week dosing regimen, without compromising the safety, efficacy and chemistry, manufacturing and control (CMC) attributes of NVG-111. Several formats were designed and evaluated and the Company successfully generated a first in class ROR1 targeting half-life extended TCE that maintains the functional and biophysical properties of the clinically promising NVG-111. Systematic evaluation suggests careful selection of human leukocyte elastase (HLE) is critical for the development of a molecule with good yield, biophysical characteristics and potency. The selected ROR1 HLE-TCE supports weekly administration whilst maintaining potency at sub-nanomolar concentrations, properties which differentiate it from other TCEs in development. Investigational New Drug (IND) enabling studies with NovalGen’s first in class ROR1 targeting HLE-TCE will conclude in 2023, supporting the initiation of a Phase I clinical trial in ROR1 hematological malignancies.

Abstract Title: A FVIII-Mimetic Bispecific Antibody with an Embedded Self-Regulation Mechanism Reduces the Risk of Prothrombotic Events for the Treatment of Haemophilia A. https://ash.confex.com/ash/2022/webprogram/Paper169482.html

Session Title: 802. Chemical Biology and Experimental Therapeutics I

Session date and time: Saturday, December 10, 2022; 2:00 PM - 3:30 PM
Presentation Time: 2:45 PM

Session room: Ernest N. Morial Convention Center, 353-355

Publication Number: 274

Presenting Author: Vincent Muczynski

Market approval of emicizumab, a Factor VIII (FVIII) mimetic bispecific antibody (bsAb) simultaneously binding coagulation Factor IX (FIX) and Factor X (FX), has significantly changed the treatment paradigm for haemophilia A patients. In contrast to FVIII, emicizumab is constitutively active and cannot be “turned off” by the natural feed-back loop of the clotting cascade mediated by activated protein C (APC) and therefore remains in a permanent procoagulant state. Consequently, emicizumab is associated with a high incidence of thromboembolic events and thrombotic microangiopathies, particularly when combined with activated prothrombin complex concentrates. NovalGen has developed a next-generation FVIII-mimetic antibody equipped with a physiological self-regulation mechanism that can inactivate the bsAb when sufficient coagulation has occurred to sustain a stable clot and prevent the progression of thrombotic events may, therefore serve as a safer therapeutic option for haemophilia A patients. This study heralds a new class of therapeutics for haemophilia A with a self-regulating off switch designed to enhance safety without compromising efficacy.

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Further information

JW Communications

Julia Wilson
Tel. +44 (0) 7818 430877
Email: juliawilsonuk@gmail.com

About NovalGen
NovalGen is a privately held clinical stage immuno-oncology company developing breakthrough bispecific therapies that can safely harness the immune system to fight cancer, with the aim of creating life-saving new treatments for people with cancer. Alongside this, we are building out our auto-regulation platform that can be applied to other drugs for indications outside of oncology, such as haematology as well as other immunotherapy indications, including cell-based therapies such as Chimeric Antigen Receptors (CAR-Ts).

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 hematologic malignancies and solid tumors using our breakthrough bispecifics technology.

About Chronic Lymphocytic Leukemia (CLL)
CLL is the most common form of leukemia in the Western world and is a type of cancer that begins in the bone marrow. The disease occurs due to a mutation in B lymphocytes, a type of immune cell that fights infection. CLL cells do not fight infection like normal lymphocytes and, over time, the uncontrolled growth of CLL cells in the marrow leads to an increase in the number of CLL cells in the blood.

About Mantle Cell Lymphoma (MCL)
MCL is a cancer of the lymphatic system and is an often-aggressive type of non-Hodgkin lymphoma beginning in the B lymphocytes within the lymph node mantle zone. These B lymphocytes are ineffective in fighting infection and progress to build up in the lymph nodes. If left undiagnosed or uncontrolled over time, the cells can spread to and build up in other parts of the body such as bone marrow and spleen.

About Haemophilia A
Haemophilia A is an inherited bleeding disorder in which the blood does not clot normally. People with Haemophilia A will bleed more than normal after an injury, surgery, or dental procedure. This disorder can be severe, moderate, or mild. In severe cases, heavy bleeding occurs after minor injury or even when there is no injury (spontaneous bleeding). Bleeding into the joints, muscles, brain, or organs can cause pain and other serious complications. In milder forms, there is no spontaneous bleeding, and the disorder might only be diagnosed after a surgery or serious injury. Haemophilia A is caused by having low levels of a protein called factor VIII. Factor VIII is needed to form blood clots. The disorder is inherited in an X-linked recessive manner and is caused by changes in the F8 gene.