Small World
A rundown of the latest developments and approvals in the world of small molecules drugs manufacturing.
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In a recent article, Mirit Eldor, Managing Director, Life Sciences Solutions, Elsevier, wrote: “In small molecule discovery, predictive retrosynthesis combines high-quality reaction data with AI to find structural or chemical patterns that correlate with specific compound properties and accelerate synthesis planning of novel molecular entities.”
It seems the oldest drug modality is as adaptable as its more modern counterparts when it comes to the uptake of AI technology in drug discovery, but what else have the small molecules stakeholders and manufacturers been up to? Here’s a roundup of recent announcements.
Lilly-Cambrex collab
Cambrex has entered into a strategic agreement with Eli Lilly and Company to support the manufacturing needs of Lilly's biotech collaborators through its Catalyze360 and ExploR&D programs. This partnership aims to provide comprehensive development and manufacturing services, leveraging Cambrex's expertise in drug substance and product development. Cambrex’ Brandon Fincher said, “Our Longmont facility offers all services required to advance early stage small molecules into the clinic with speed, flexibility and scientific excellence. We look forward to propelling Lilly Cataylze360 collaborators forward on an efficient path to success with their products.”
Modulate to innovate
Dewpoint Therapeutics and Mitsubishi Tanabe Pharma Corporation have initiated a research collaboration to develop a small molecule condensate modulator targeting TDP-43, a protein implicated in amyotrophic lateral sclerosis (ALS). This partnership aims to address the underlying pathology present in approximately 97 percent of ALS patients. Under the agreement, Mitsubishi Tanabe Pharma holds an option for a global license to develop and commercialize the novel TDP-43 modulator. The deal is valued at up to $480 million, with Dewpoint receiving upfront payments and additional development and commercial milestone payments.
China in UCB’s hands
UCB has finalized the sale of its mature neurology and allergy business in China, including brands such as Keppra, Vimpat, Neupro, Zyrtec, and Xyzal, along with its Zhuhai manufacturing facility, to CBC Group and Mubadala Investment Company for $680 million. The divested assets will be managed by NeuroGen Pharma, a new entity established by the purchasers. UCB CEO Jean-Christophe Tellier said, “UCB has been dedicated to improving the lives of patients in China for nearly three decades, building a foundation of trust and delivering treatments that address critical health needs. This agreement allows us to accelerate our commitment to innovation, focusing on bringing new and impactful therapies to the Chinese market through strong partnerships.”
Novartis on the Hunt
Novartis has entered into a global licensing and collaboration agreement with PTC Therapeutics for PTC518, an investigational oral therapy targeting Huntington's disease. The deal includes a $1 billion upfront payment to PTC, with potential additional payments up to $1.9 billion based on development, regulatory, and sales milestones. Novartis will assume responsibility for the development, manufacturing, and commercialization of PTC518 following the completion of the ongoing phase II PIVOT-HD study, expected in the first half of 2025. This collaboration aims to advance a promising treatment for Huntington's disease, a progressive neurodegenerative disorder with limited therapeutic options.
Small, but highly selective
UK-based Duke Street Bio has initiated a phase I clinical trial for DSB2455, a highly selective PARP1 inhibitor, by dosing the first patient with solid tumors. This first-in-human study aims to evaluate the safety, tolerability, and efficacy of DSB2455 as a monotherapy and in combination with other anti-cancer agents. Unlike first-generation non-selective PARP1/2 inhibitors, DSB2455 targets PARP1 with high specificity, potentially reducing hematological toxicities and enhancing therapeutic outcomes, especially in tumors with homologous recombination deficiencies such as BRCA mutations. CMO Dónal Landers said, “We believe that DSB2455 exhibits the optimal potency and selectivity profile to enhance efficacy and safety and may offer the potential to enable combination approaches with chemotherapy and radiotherapy.”
A new AMR avenue?
Researchers at the Centre for Genomic Regulation have discovered that Escherichia coli can modify its ribosomes in response to antibiotics such as streptomycin and kasugamycin. By removing specific chemical tags from ribosomal RNA, the bacteria alter the antibiotic binding sites, reducing drug efficacy and enhancing resistance. This finding reveals a novel mechanism of antibiotic resistance, distinct from known genetic mutations or drug efflux strategies. The team utilized advanced nanopore sequencing to observe these modifications in their natural context. Understanding this adaptive process could inform new strategies to combat the growing threat of antimicrobial resistance.
AZ caps off a strong year
AstraZeneca's phase III CAPItello-281 trial demonstrated that combining TRUQAP (capivasertib) with abiraterone and androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer, compared to abiraterone and ADT with placebo. While overall survival data are still maturing, an early trend suggests potential improvement. The safety profile of the combination was consistent with known profiles of the individual treatments. These findings mark the first instance of an AKT inhibitor combination benefiting this specific prostate cancer subtype. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These results show for the first time, that adding an AKT inhibitor to a standard-of-care therapy can provide benefit to patients with a biomarker of PTEN-deficient metastatic hormone-sensitive prostate cancer. By targeting a key driver of the disease, we have been able to improve upon current therapies and demonstrate the potential role of this combination in an area of critical unmet need. It will be important to see greater maturity in key secondary endpoints including overall survival.”
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