Tim Knotnerus

AgomAb Therapeutics - Biotechnology

Profile

ABOUT TIM KNOTERUS
Tim is CEO and member of the Board of Directors of Agomab, a Belgian biotech company focusing on growth factor biology and developing therapeutics for fibrotic indications. Together with the team, he has raised around $140M from top US and EU investors since joining Agomab in 2019. Prior to Agomab, Tim held the position of VP Corporate Development at AM-Pharma where he and the team executed a Phase IIb trial in patients with acute kidney injury, secured a $600M option-to-buy deal with Pfizer and raised significant private financing rounds. Prior to that, Tim was a Senior Associate at Aescap Venture, a VC fund investing in European medical companies. During 2022, Tim received the CEO of the year award by European Lifestars and was selected as an Endpoints 20 under 40 and In Vivo rising leader. He holds an executive MBA from IMD, where he was named Valedictorian, and earned two Master degree programs from Utrecht University.

ABOUT AGOMAB THERAPEUTICS
Agomab is translating a deep expertise in growth factor biology to pioneer and develop novel treatments that aim to resolve fibrosis, repair tissue structure and restore organ function. Combining new scientific insights with robust drug development and a long-term corporate vision, we are building a broad clinical pipeline of differentiated programs with disease modifying potential in organ failure and fibrotic diseases.

WHY TARGET GROWTH FACTOR PATHWAYS FOR FIBROTIC INDICATIONS?
Fibrotic processes are the underlying factors in a variety of difficult-to-treat diseases, resulting in progressive organ failure. For most fibrotic diseases, blocking inflammatory events only, e.g. by inhibiting cytokine signaling, is not expected to deliver substantial disease stabilization or reversal. Because inflammation and fibrosis are such complex and interconnected processes, one needs to identify assets with broad mode of actions able to address redundancy across multiple pathways.

Growth factor pathways have evolved to coordinate broad morphogenic and tissue repair programs, and can be leveraged to profoundly alleviate tissue injury, fibrotic remodeling, and organ failure. Because growth factors possess such broad activity, it is important to have a deep understanding about how to modulate them, and how to devise small molecules or biologics to do this.

This is where we leverage our deep understanding of growth factor biology and employ smart small molecules targeting the TGF_ pathway and agonistic antibodies targeting the HGF/MET pathway. The company’s pipeline consists of unique assets with a novel mode of actions against well-validated and potentially disease modifying targets with the aim to repair tissue injury, resolve fibrosis and restore organ function in patients with high unmet medical need.

WHY ARE WE TARGETING THE TGF-§ PATHWAY?
TGF-§ is a core regulator of fibrogenic pathways and is considered the major driver of fibrosis. Once activated, TGF-§ coordinates the conversion of quiescent fibroblasts into myofibroblasts in addition to initiating the direct transcription of pro-fibrotic genes.

Inhibition of the intracellular kinase domain of the TGF-§ receptor (ALK-5) is desirable in the treatment of fibrotic disorders for its potential in blocking canonical and non-canonical TGF-§ signaling. Though several TGF-§ inhibitor approaches have been stalled by systemic toxicity levels, specific ALK-5 inhibitors have shown strong anti-fibrotic effects in the gastrointestinal tract, lungs, and liver.

Armed with this knowledge, we are creating organ-restricted ALK-5 inhibitors to leverage blockade of the TGF-§ pathway while avoiding systemic exposure.

WHY ARE WE TARGETING THE HGF/MET PATHWAY?
HGF is a pleiotropic growth factor of mesenchymal origin that mediates a variety of biological processes, including cell proliferation, cell survival, cell motility and cell differentiation. The high affinity receptor for HGF is the tyrosine kinase MET. This receptor is mainly expressed by epithelial and endothelial cells but can also be found in other cell types such as muscle, neuronal and hematopoietic cells as well as in the majority of myofibroblasts.