q pharm hiv june 2014
TRANSCRIPT
The human immunodeficiency virus (HIV)
Quantum Products HIV
- First in class compounds, novel MoA (HIV MA/p17 matrix protein, entry- and late- stage inhibitors (Quantum + Drexel Medical college.us)
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Quantum Products HIV - novel MoA
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- The most conservative HIV target (shared with SIV and FIV) - less drug resistance potential
- There are no human analogues - less tox
- Multi-functional protein - new treatment opts
Quantum Products HIV - novel MoA
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- Binding is proven by SPR, competition and mutagenesis studies
- Q-compounds active against HIV in vitro
- HIV MA has been crystallized, Q-compounds soaked into the protein, the studies are under way
Quantum Products HIV - novel MoA
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- Treatment with HDBQP-031 yields escape mutants A44S and R57I in HIV-MA
HIV MA/p17 matrix protein inhibitors
Indication HIV treatment, prophylaxis
Dosage form Oral tablet
Primary end-point Virus load suppression
Safety Compatible with life-long treatment
Product differentiation- One of the most conservative targets in HIV genome (low drug resistance potential)!- New mechanism of action (no competition, possible new treatment options)!- Low expected daily dosage
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Quantum Products HIV MA - No strong academic competition (best mols
>10uM); Boehringer Ingelheim just published
- MedChem optimization, preliminary ADMET looks good, PC nomination imminent
- IP rights belong to Quantum (3 PCT, more to come, lots of mols)
- Skolkovo matching grant up to phase II.ru
- Looking for in-licensing or co-development options.worldwide
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- Physics based molecular modeling tools to overcome specificity problems
- Challenging targets including PPI
Quantum Technology
Quantum Technology
Efficient fragment based lead generation (LE>0.3, EC50<1uM)
Binding free energies calculation tools capable to dock small mols
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docking of fragment #1
docking of fragment #2
ligand designed as fused fragments #1 and #2
Quantum Pharmaceuticals "MoA
- Founded 2004
- Discovers innovative drugs against most challenging targets using proprietary first principles, molecular modeling and systems biology tools
- Collaborates with top academia (MIPT.ru, UC Davis.us, Texas.us, Drexel Medical School.us, MIT.us etc)
- Medical chemistry and biology (InPheno.ch, HDbio.cn, Wuxi.cn, Nanosyn.us etc)
- Works with governments (Skolkovo.ru, MTI.ru, collab+NIH.us) and private investors
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Quantum Products "HIV preclinical overview
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Biological activity
Equilibrium MA/p17 Kd - <1uM SPR, >2hrs off-time; PIP2 competition assay
Cellular efficacy, EC50
- <1-100nM (almost no variance between HIV clades)!
- both early and late stage inhibition!- few compound are equipotent MA
and RT inhibitors
CC50 >150uM
Mouse PKt1/2 2.7h (mice)
Cmax (PO, 10mg/kg bw) 1.1uM
acute tox, LD50 >3g/kg
- Escape mutant is expected (days)
- Covalent binders are being studied for even better dosage
- Chronic toxicity of the few lead compounds - 2014
