CULVER CITY, CA--(Marketwired - December 10, 2013) - Indi Molecular, which pioneered a synthetic replacement for antibodies, today announced that it has raised an additional $300,000 from a new investor, Asset Management Ventures. With this investment, the company has expanded its seed round to a total of $1.8 million. The round was led by InterWest Partners and joined by several angel investors. The funds are being used to further develop PCC (protein catalyzed capture) agent technology: a breakthrough process that produces synthetic peptide molecules capable of binding interactions that are equivalent or superior to molecular antibodies. The company also announced that it has published three new papers in recent weeks, appearing in Angewandte Chemie, PLOS One and ACS Nano. All three papers were written in collaboration with researchers at the California Institute of Technology (Caltech), with the goal of furthering the development of PCC technology.
"We are pleased to announce significant progress towards our goal of replacing the monoclonal antibody with PCC agents -- a new class of chemically defined smaller molecules with superior overall performance," said Albert A. Luderer, Ph.D., CEO, Indi Molecular. "We are also delighted to welcome Asset Management Ventures and Lou Lange as investors in Indi Molecular. With our seed round complete and our ongoing research collaborating with Caltech producing three published papers in a single month, Indi Molecular is demonstrating substantial progress towards further developing PCC agents. We believe they will play an important role in enabling a new generation of sophisticated diagnostics -- and rationally designed therapeutics and biological tools."
PCC agents are molecules designed to exhibit the attractive features of monoclonal antibodies, plus additional features that can enable applications in the commercial spaces of in vivo imaging, therapeutics, in vitro diagnostics and biological tools. PCCs have several advantages over antibodies, including lower cost, faster development and greater specificity.
"Indi Molecular's vision for replacing monoclonal antibodies with a highly flexible synthetic alternative holds tremendous promise," said Louis Lange, M.D., Ph.D., partner, Asset Management Ventures. "I am delighted to work with Al, Jim and the rest of the team to bring this unique technology to market."
PCC agents are comprised of short chain peptide molecules, each of which contributes binding affinity and selectivity characteristics towards a protein of interest. A differentiating aspect of the PCC agent technology is that the protein target itself provides a catalytic scaffold for assembling and coupling the short chain peptides -- choosing across very large peptide libraries to find only those ligands that couple onto its surface in a highly selective fashion.
"Each of these papers shows the significant advantages of PCC agents over antibodies in a particular realm; taken together, they demonstrate the tremendous flexibility and promise of PCC technology," said Jim Heath, Ph.D., co-founder and Board member, Indi Molecular; Gilloon Professor, Caltech; and co-author of all three papers. "Working together, researchers at Indi Molecular and Caltech have shown how PCC agents behave in three very different situations: targeting a highly specific region of a selected protein that is an important cancer drug target; diagnosing HIV with unique temperature stability and; detecting signs of anthrax at extraordinarily low concentrations."
Three Recent Publications
The most recent publication, a communication in Angewandte Chemie, researchers describe how PCC agents can be targeted at a highly specific region (an epitope) of a selected protein. Such epitope targeting is possible with monoclonal antibodies, but not with any other protein capture agent approach. The researchers targeted a region of the protein Akt2, which is an important drug target in cancer. Traditional approaches to Akt2 can lead to the confounding result that the protein is further activated, rather than inhibited. The researchers from Caltech and Indi Molecular used an epitope targeting strategy to design PCC agents against what would normally be considered an undruggable site of Akt2. Researchers choose it because when the targeted site is phosphorylated (a natural biological process), the enzymatic activity of Akt2 is increased 10-fold. The group reported on two PCC agents -- one that activated Akt2, and a second one, which inhibited it. Furthermore, the PCC agents exhibited a high selectivity for Akt2 relative to two very similar proteins, Akt1 and Akt3, thus demonstrating a very high level of selectivity that is hard to achieve even with monoclonal antibodies.
In the second article, in PLOS One, researchers report on the development of a small panel of PCC agents designed to detect specific anti-HIV1 antibodies in a blood-based diagnostic assay. For many HIV-infected patients, the only detectable signature of infection is the antibodies that the individual patient has generated against the virus. This presents a diagnostic challenge in that each patient may generate antibodies that are slightly different from every other patient. The team of Indi Molecular and Caltech researchers approached this challenge by using a small fragment of the HIV virus surface, known as glyco-protein (GP)41, as a common starting point for three different PCC agents. In a comparison study of a cohort of HIV-infected patients, the PCC agent cocktail was shown to be between 50% to 800% times more effective than the gold standard diagnostic test, which is based upon biologic reagents. Furthermore, these PCC agents could be safely stored at near 60 degrees C (140 degrees F) for almost 3 months. This type of stability points to the potential use of PCC agent diagnostic assays in developing world healthcare applications, where developed world infrastructure, such as refrigeration chains to support antibody-based diagnostics, are not always available. The Bill and Melinda Gates Foundation supported this work.
The third paper, published in the journal ACS Nano, describes the development of a PCC agent designed to detect the protein protective antigen (PA). PA is associated with the bacteria bacillum anthracis that causes the lethal disease of anthrax. The work was the product of a 4-way collaboration between Caltech, Indi Molecular, the Gwangju Institute of Science and Technology (GIST), and the Army Research Labs. The goal was to develop a field-stable approach for detecting PA at trace levels in environments that range from drinking water to blood. The group developed a PCC agent that selectively captures PA, and then integrated that detection onto a nanostructured gold surface to build a highly sensitive and selective electrochemical PA detector that could detect as little as 2 picoMolar concentrations of PA in 1% serum. That PCC agent was shown to be stable when stored at temperatures up to 65 degrees C (150 degrees F).
1. Farrow B; Hong SA; Romero EC; Lai B; Coppock MB; Deyle KM; Finch AS; Stratis-Cullum DN; Agnew HD; Yang S; Heath JR. A chemically synthesized capture agent enables the selective, sensitive and robust electrochemical detection of Anthrax Protective Antigen. ACS Nano. 7, 9452-9460 (2013). DOI: 10.1021/nn404296k.
2. Pfeilsticker JA; Umeda A; Farrow B; Hsueh CL; Deyle KM; Kim JT; Lai BT; Heath JR. A cocktail of thermally stable, chemically synthesized capture agents for the efficient detection of anti-gp41 antibodies from human sera. PLoS ONE 8: e76224. DOI:10.1371/journal.pone.0076224.
3. Nag, A; Das S; Yu MB; Deyle KM; Millward SW; Heath JR. A Chemical Epitope Targeting Strategy for Protein Capture Agents: The Serine 474 Epitope of the Kinase Akt2. Angew. Chemie Int. Ed. Engl. (published online 11/2013). DOI:10.1002/anie.201305882.
About Indi Molecular
Indi Molecular is an emerging life sciences company that is developing a synthetic class of diagnostic and therapeutic agents with antibody-like properties: protein-catalyzed capture agents. PCCs were created in collaboration with the California Institute of Technology using "click chemistry," a synthetic process that allows scientists to permanently join ("click") together molecular components with unusual precision and stability. PCCs offer the promise of superior stability, lower cost and faster creation compared to monoclonal antibodies, the current standard for identifying biomarkers in most diagnostics platforms -- and in many therapeutic uses.
The company launched as a spinout from its parent company Integrated Diagnostics (Indi) in 2013 with a $1.8 million seed round led by InterWest Partners together with several angel investors. For more information visit www.IndiMolecular.com
Asset Management Ventures
Over nearly half a century, Asset Management has provided early-stage financing for ground-breaking companies. Today, the firm continues its diversified investing approach by deploying capital in early-stage companies focused on therapeutics, digital health, big data analytics and mobility. The firm is run by a leadership team comprised of former operators with expertise in science, engineering and medicine.