At least 12 companies are developing macrocycle and constrained-peptide synthesis technologies. (A) Disclosed financings; (B) Formed following the merger of Tranzyme Inc. with Neokima Inc. in 2003; Source: BCIQ: BioCentury Online Intelligence; company press releases and websites

Company

Platform technology

Lead program

Founded

Raised (A)

Aileron Therapeutics Inc.

Alpha-helical stapled peptides

ALRN-5281, a preclin long-acting growth hormone- releasing hormone (GHRH) agonist for adult growth hormone (GH) deficiency, HIV lipodystrophy and GH-deficient abdominal obesity

2005

$60M

Bicycle Therapeutics Ltd.

Phage display of bicyclic peptides

Undisclosed preclin programs

2009

$6.1M

Encycle Therapeutics Inc.

Amphoteric cyclization

Undisclosed preclin programs

2012

$1M

Ensemble Therapeutics Corp.

DNA-programmed chemistry for macrocycle synthesis

Preclin antagonist of interleukin-17 (IL-17) for autoimmune/inflammatory diseases

2004

$38.5M

Lanthio Pharma B.V.

Lanthionine constrained peptides produced in Lactococcus lactis

Preclin lanthionine-Ang(1-7) peptide targeting the MAS receptor to treat acute lung injury (partnered with Tarix Pharmaceuticals Inc.)

2010

$784K

Oncodesign S.A.

Nanocyclix medicinal chemistry

Disclosed preclin programs include inhibitors of kinases including leucine-rich repeat kinase 2 (LRRK2) to treat Parkinson's disease (PD) (partnered with Ipsen Group (Euronext:IPN; Pink:IPSEY); FMS-like tyrosine kinase 3 (FLT3; CD135) and germ cell associated 2 (haspin) for cancer; neurotrophic tyrosine kinase receptor (TRK) for pain; and CDC-like kinase (CLK) for CNS indications

1995

$4.6M

Pepscan Therapeutics B.V.

CLIPS (chemical linkage of peptides onto scaffolds)

Disclosed preclin programs include an HIV-fusion inhibitor (partnered with Johnson & Johnson (NYSE:JNJ))

2000

$14.8M

PeptiDream Inc.

mRNA display of modified cyclic peptides containing natural and unnatural amino acids

Undisclosed preclin programs

2006

ND

Polyphor Ltd.

MacroFinder macrocycle platform and PEMfinder (protein epitope mimetics) cyclic peptide platform

POL6326, a CXC chemokine receptor 4 (CXCR4) inhibitor in Ph II to treat cancer using hematopoietic stem cell (HSC) transplantation

1996

ND

Protagonist Therapeutics Inc.

Disulfide rich peptides (DRPs)

Disclosed preclin programs include orally stable interleukin-6 (IL-6) peptide antagonists and oral DRPs for inflammatory bowel disease (IBD)

2006

$9M

Ra Pharmaceuticals Inc.

mRNA display of modified cyclic peptides containing natural and unnatural amino acids

Preclin plasma kallikrein inhibitor for hereditary angioedema (HAE)

2008

$27M

Tranzyme Inc. (NASDAQ:TZYM)

MATCH (macrocyclic template chemistry)

TZP-102, an oral ghrelin agonist in Ph II for diabetic gastroparesis

2003 (B)

$140M