• Singapore
  • 9 July 2012
  • Opinion
  • By Dr Takeshi Yura

Integrated drug discovery fuels healthy outcomes

Updated on 9 July 2012

In the area of anti-infectives, AMRI licensed a series of potent, small molecular antibacterial compounds with a novel mechanism of action to a large biotechnology company in January 2011. AMRI used multi-drug resistant clinical isolates to screen its own natural product libraries for samples containing antibiotics. Classical antibacterial microbiology and human cell line toxicity assays were used by AMRI to select samples for the purification and structural elucidation of active compounds. The company conducted optimizations of fermentation conditions and downstream isolation processes. AMRI designed in vivo efficacy and pharmacokinetic studies and outsourced the in-life phases to CROs with a reputation for providing high quality in vivo work among the antibacterial community. In addition, AMRI designed and conducted mechanism-of-action studies.

In the area of CNS, a large pharmaceutical company licensed an entire AMRI technology platform and in collaboration with AMRI has progressed three compounds into human clinical trials. One compound, which is designed for the treatment of major depressive disorder (MDD), is furthest along in phase II human clinical trials. During this project, AMRI's medicinal chemistry team performed lead optimization to identify potent triple reuptake inhibitors suitable for advancement to human clinical trials for treatment of MDD. The synthesis of more than 2,000 novel compounds has led to the filing of more than 10 patent applications covering composition of matter and chemical method of preparation where AMRI scientists played a major role as inventors. Lead compounds were developed and advanced that met the target product profile (TPP), which defined safe and effective lead agents for treatment of MDD. Lead compounds and preclinical development candidates demonstrated excellent pharmacokinetics / pharmacodynamics (PK/PD) and target engagement data and good safety in animal toxicology studies. In early stages, AMRI defined a lead optimization screening paradigm and TPP and identified a preclinical development candidate.

AMRI's CNS strengths are backed by a history of success regarding its former proprietary drug discovery and development activities. Within its current portfolio, several programs are available for partnering and out-licensing. Each program has a business strategy to differentiate them from the existing standard of care. AMRI's goal is to find partners with the ability to drive these programs through development and to commercial success.
For example, AMRI is seeking a partner to progress development of its 5-HT3 partial agonist program. AMRI's advanced compounds are mechanistically differentiated from existing medications targeting this receptor. AMRI has identified its first preclinical candidate, ALB-137391(a), and back-up candidates that are available for partnering.

AMRI also seeks a partner for its 5-HT6 antagonist research program targeting treatments for cognitive impairment in Alzheimer's disease, schizophrenia and orphan diseases. A leading candidate compound and multiple back-up compounds are available for advancement.

Additionally, AMRI is seeking a partner for its glycine transporter-1 (GlyT-1) inhibitor R&D program. AMRI's lead series is differentiated from advanced clinical compounds through a preferred competitive inhibition mode of action and higher potency. In preclinical studies, these compounds show excellent potency in animal efficacy models and without the side-effect profile of traditional anti-psychotic medications.

 

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