BPS 2015
A Platform Technology for Drug-Like Peptides
Kenneth Gruber
President/Chief Scientific Officer, Tensive Controls, Inc.
ABSTRACT
In the age of proteomics, there is increasing need for an approach to enhance the therapeutic activities of peptides, especially those with regulatory activities applicable to cancer and infectious diseases. Peptides have high activity and specificity, and low non-specific toxicity; desirable characteristics for a drug. However, their lack of oral activity and blood-brain-barrier transport, and their rapid metabolism/excretion greatly reduces clinical utility.
We developed a platform technology that transforms natural or synthetic peptide sequences into a “drug-like†molecule: orally active, with the ability to cross the blood-brain barrier, and having an in vivo half-life of hours. The “apparent†transport effects appear to be due to the peptide acting as a substrate of the multispecific bile acid transporter, similar to cyclosomatostatin and several other cyclized peptides. Using a progressive series of melanocortin peptide analogs and solution NMR spectroscopy, we defined the two critical structural aspects of the technology: ideally a side-chain cyclized peptide that is maintained in a β-conformation through intramolecular hydrogen bonds, and a C-terminal dipeptide extension composed of non-polar residues.
The platform can be used in several ways: cyclization of the peptide sequence of interest plus a C-terminal extension, or (if the biological activity resists cyclization) attachment of the peptide to the N-terminus of a cyclized “transporter†sequence. In the later approach, the hybrid peptide maintains the transport/drug-like features of the cyclized transporter.
As proof of concept, we applied our platform to four types of peptides with potentially important therapeutic activity. These were an anti-cancer cachexia agent (preventing the “wasting†of body mass in many diseases), an anti-angiogenic/anti-proliferative anti-cancer agent, several antiviral peptides, and a hybrid anti-microbial/anti-biofilm peptide for hospital-associated antibiotic-resistant infections. With latter, the anti-microbial peptide was cyclized, while the anti-biofilm sequence required an alpha helix for activity. Combining both peptides into a single structure preserved and even enhanced their respective microbiological activities, producing a drug candidate for in vivo testing.
Rodent and canine safety studies demonstrated that therapeutic peptides produced by the platform were devoid of cardiovascular, serological or blood chemistry side-effects. A CMO has already made several of the above therapeutic peptides to a cGMP standard, and these peptides maintain stability in FDA standard studies. Several of the peptides from the platform are in formal FDA pre-clinical development. Thus, the technology appears to be a commercially feasible approach to convert peptides into drug-like agents.
BIO
Information for BPS Presenters
The Boulder Peptide Foundation was established to further the science and knowledge of peptide technology to develop novel therapeutics, biomaterials, medical diagnostics and other beneficial uses for mankind. As part of this goal we run several programs to support career advancement, seminars and educational events. Join us on our mission to expand the applications of peptide science.
Information for BPS Presenters
The purpose of the Boulder Peptide Symposium is to encourage sharing of information related to peptide therapeutic development with an emphasis on the technical, scientific and regulatory aspects of the pharmaceutical development. Presentations that demonstrate original thinking or share experiences from case studies in product development shall receive priority over others.
The Boulder Peptide Symposium offers multiple opportunities for participants to present.
Oral Presentations in Scientific Sessions
The session topics for Scientific Program are Peptides in the Clinic, Drug Delivery, Chemistry of Complex Peptides, Spotlight on Discovery, and Peptide Showcase. Abstracts may be submitted via the Apply to Present page on the website. Submissions will be reviewed by the Scientific Advisory Board on a monthly basis and the speaker will be notified of a decision.
Presentation length: Format is 25-30 minutes slide presentation with 5-10 minutes for Q&A, with the exception of Peptide Showcase talks which are 10 minute slide presentations with 5 minutes for Q&A. Please confirm with your session chair to confirm the exact presentation length.
Invited Speakers: Speakers are requested to supply their presentation details 30 days after receiving an invitation to present.
Program Book Deadline: Final abstract and title must be provided no later than September 1st. No changes to the program are possible after this date.
Presentation Format: Oral presenters please provide your presentation slides to the A/V table on the day of your presentation.
Lodging: All speakers are requested to reserve their own room. Discount rates at the conference hotel are available until August 16th.
Registration: All speakers, excluding sponsored presentation speakers, receive a complimentary registration upon approval of the abstract.
Peptide Showcase Description
The Peptide Showcase is an opportunity for an individual or company to “showcase” new ideas, technology and pipeline assets. Priority shall be given to presentations from biotech and startup companies. Service providers and vendors are not eligible. Speakers in the session receive a complimentary event registration.
Posters
Posters can be presented on any topic relevant to peptides including original research, innovative products and technologies.
Eligibility- Any attendee (from academia, industry, biotech or vendor/sponsor) can present a poster. The presentation must contain original scientific thinking. To submit a poster go to the Submit a Poster link from the meeting menu. All submissions are reviewed on a rolling basis and will be notified of approval. September 1st is the last day to submit a poster abstract. Approved posters are published on the BPF website.
A 30 ” x 40″ board shall be provided with thumb tacks. Board will be on an easel and can be rotated for either landscape or portrait formats. Once you apply for a poster, you will get email confirmation that your poster was accepted. The poster session and number assignments will be emailed one week before the Symposium.
Poster boards shall be available for display from 8am to 8pm the day of your assigned poster session. See the program agenda for the poster session schedule.
Public Release
Every presentation at the Boulder Peptide Symposium is automatically recorded. Speakers are required to give consent for sharing of the presentation video with the peptide community.