Product Summaries

SQ109 THERAPEUTIC

Status: Phase I clinical trials

Background: Developed in partnership with the NIH, SQ109 is a new diamine anti-TB drug. It could replace one or more drugs of the existing first-line TB drugs in intensive phase regimen of the WHO-recommended Directly Observed Therapy (DOT).

Product Profile: SQ109 is a small molecule anti-TB drug with a novel structure and mode of action identified from a library of over 63,000 compounds.  SQ109 has the following properties:

• Orally bioavailable, concentrates in lung and spleen
• Long half-life
• High potency against Mycobacterium tuberculosis in vitro and in vivo
• Effective as a single drug in murine models of TB infection at 10 mg/kg
• Effective against profoundly drug-resistant TB in vitro
• Has a high degree of specificity for Mycobacteria
• Exhibits synergistic activity with the first-line drugs Rifampicin and Isoniazid in vitro and in vivo.
• Shortens treatment time to cure by 25% in experimental animal models of TB

R&D Milestones:  SQ109 has completed all IND-directed preclinical toxicology, pharmacology, and safety studies in two animal species. The IND was filed with the U.S. FDA in August 2006.

Market Opportunity:  For more information, please see our SQ109 Backgrounder.

SQ609 THERAPEUTIC

Status: IND-directed pre-clinical toxicology and pharmacology

Background: The drug discovery program at Sequella identified a new class of antibiotic compounds, dipiperidines, with promising in vitro and in vivo anti-TB activity.  SQ609 was identified as a lead candidate in this series. 

Product Profile Attributes: 

• Potent in vitro activity against M. tuberculosis
• Kills M. tuberculosis by interfering with cell wall biosynthesis
• Low in vitro toxicity in cultured mammalian cells
• Orally bioavailable
• Antimicrobial activity in vivo in two different mouse models of TB
• Significantly prolongs therapeutic effect after the withdrawal of drug therapy in mice
• Favorable in vitro safety pharmacology profile
• Has antiviral activity against SARS in vitro.

For more information, please see our SQ609 Backgrounder.

SQ641 THERAPEUTIC

Status: Formulation Development

Background: Sequella is developing SQ641, a drug candidate with potent activity against Mycobacterium tuberculosis (MTB), multi-drug resistant strains of MTB, and non-tuberculous Mycobacteria (NTM). SQ641 is a semi-synthetic antibiotic and belongs to the class of nucleoside-based capuramycins.  In addition to its remarkable antibiotic properties, it acts so quickly that it is highly effective in preventing the development of drug-resistant mutants in vitro.

Product Profile Attributes:

• kills MTB much faster than any of the existing anti-TB drugs, including INH and rifampin (RIF)
• is active against all strains of multidrug-resistant TB  (MDRTB) tested to date
• has an exceptional 55 hr post antibiotic effect (PAE) against MTB
• shows strong synergy with EMB, streptomycin, and SQ109, Sequella’s lead antitubercular drug in clinical trials
• is highly effective in preventing development of drug resistant mutants in MTB
• has excellent in vitro activity against M. avium complex (MAC) bacteria, M.abscessus,and M.kansasii
• acts synergistically with other anti-mycobacterial agents against NTM.

For more information, please see our SQ641 Backgrounder.