Dewpoint and Mitsubishi Tanabe to advance small molecule condensate modulator for ALS

Privately-held Dewpoint Therapeutics, a Boston, USA, biotech developing therapeutics by targeting biomolecular condensates, has entered into a strategic research collaboration with Japan’s Mitsubishi Tanabe Pharma Corporation (MTPC).

The collaboration will see the companies advance Dewpoint’s novel TDP-43 small molecule condensate modulator (c-mod) for amyotrophic lateral sclerosis (ALS).

Under the terms of the agreement, Dewpoint will receive an upfront payment and will be eligible for milestone payments based on specified near-term research and development objectives, with a total nominal deal value of up to $480 million.

Upon reaching these milestones, MTPC will have an exclusive option to license the program and assume responsibility for global clinical development and commercialization. Dewpoint will also receive tiered royalties on net sales.

'Transformative potential'

Ameet Nathwani, chief executive of Dewpoint, said: “We are delighted to collaborate with MTPC in advancing our condensate-modulating approach to address the critical unmet need in the treatment of ALS.

“This partnership underscores the transformative potential of our small molecule condensate modulator which aims to tackle the underlying pathology of ALS and related neurodegenerative diseases via a novel mechanism of action. Our c-mod was discovered and developed through Dewpoint's pioneering condensate-targeted platform.

“MTPC's unparalleled expertise in ALS, as the developer of the only US Food and Drug Administration-approved therapy for sporadic ALS, combined with its global clinical capability and expansive patient network, makes them an ideal partner. Together, we are poised to accelerate the clinical development of this innovative program and bring hope to patients facing this devastating disease.”

A leader in condensate biology, Dewpoint has discovered a small molecule that addresses the mislocalization of the TAR DNA-binding protein 43 (TDP-43), a critical splicing factor implicated in several neurodegenerative diseases and a key pathological feature present in more than 97% of ALS patients. TDP-43 abnormally accumulates in membrane-less cytoplasmic structures, known as biomolecular condensates, leading to neuronal dysfunction in ALS patients.

Using its high-content, high-throughput screening approach, Dewpoint identified a c-mod capable of mitigating these pathological TDP-43 condensates by selectively departitioning TDP-43 and restoring its correct localization into the nucleus, while preserving the normal cellular stress response.

By correcting this disease-driving condensate dysfunction, the treatment restores TDP-43's normal splicing activity, promotes neuronal health and improves multiple clinically relevant ALS biomarkers in animal models.

Dr Nathwani added: “The success we’ve had so far with this c-mod in reversing ALS-associated pathology suggests that this compound may find future applications in other indications which share the TDP-43 condensatopathy.”

'Leading company in ALS therapeutics'

Masao Nawano is vice president, head of research division of MTPC, a subsidiary of Mitsubishi Chemical Group (TYO: 4188).

“ALS remains a critical area of unmet medical needs and MTPC is committed to addressing it as the leading company in ALS therapeutics,” he said.

“There are limited treatment options for ALS patients, particularly those with sporadic ALS, where no known underlying genetic cause has been established. We are excited to join forces with Dewpoint to advance this promising small molecule c-mod that takes advantage of their unique expertise and cutting-edge technologies in condensate biology.

“Together, we have the potential to deliver meaningful innovations to patients and families affected by this devastating condition.”