Boston Children's and Proteus S.A. enter partnership with Grünenthal to bring long-lasting local anesthetic through late-stage clinical trials

Proteus S.A. and Boston Children's Hospital entered an exclusive partnership with Grünenthal GmbH, a privately held family owned pharmaceutical company that specializes in pain management, for the continued development of neosaxitoxin (NeoSTX) towards a product for local anesthesia and post-operative pain management.

Proteus S.A. and Boston Children's Hospital have worked together since 2010 on the development of NeoSTX, a site-1 specific sodium channel blocker derived from cyanobacteria. The two groups will continue to actively participate in its development as part of the agreement. The deal also provides up to $85 million in upfront and development milestones plus undisclosed sales milestones and royalties.

Cyanobacteria under a microscope

"We are thrilled to be entering this collaboration with Proteus and Boston Children's Hospital", says Dr. Klaus-Dieter Langner, chief scientific officer of Grünenthal. "We believe that this project could transform an area that has lacked innovation for decades."

The problem with current local anesthetics and analgesics based on opioids is that they have a short duration of action (8 hours or less), leaving patients to cope with postoperative pain. Early animal and human data indicate that NeoSTX used in combination with local anesthetics such as bupivacaine provides markedly prolonged surgical anesthesia, relative to bupivacaine alone. NeoSTX has the potential to ameliorate the need to use the potentially addictive opioids after undergoing surgery.

Proteus uses a proprietary technology to produce and purify the NeoSTX in a clean, inexpensive and environmentally friendly process. Charles Berde, MD, PhD, chief of the Division of Pain Medicine, Daniel Kohane, MD, PhD, director of the Laboratory for Biomaterials and Drug Delivery, and their colleagues have been working with this compound for over twenty years.

"Our partnership with Proteus has produced a new and innovative approach to treating pain. Dr. Charles Berde and Dr. Daniel Kohane have researched this novel approach for decades in order to bring it to clinical trials," comments Paul Hickey, MD, anesthesiologist-in-chief at Boston Children's Hospital.

A Phase I clinical trial, building upon early work done by Proteus in Chile, was successfully conducted at Boston Children’s by Joseph Cravero, MD, principal investigator, along with the a research team in the Division of Pain Medicine. This study was performed under an Investigational New Drug (IND) Application with the FDA submitted by Dr. Berde. This dose-escalation study of 66 healthy male volunteers indicated that NeoSTX given in combination with bupivacaine provided a more prolonged block and more intense block than bupivacaine alone as measured by mechanical pain detection and mechanical touch detection. None of the volunteers experienced physiologically significant side effects within clinically relevant dosage ranges. Another piece of this study evaluated 18 subjects and compared combinations of NeoSTX plus bupivacaine with and without epinephrine. The results showed a significant prolonged block and amelioration of side effects when epinephrine was added to the combination.

The results were presented in October 2014 at the annual meeting of the American Society of Anesthesiologists and won the meeting’s prestigious Best Clinical Science Abstract award. Two papers, one in rats and one on the Phase 1 study, are in press in Anesthesiology, and are tentatively scheduled to be published online in late July or August.

"NeoSTX has the potential to provide long-acting local anesthesia, greatly improving the post-operative experience for patients," said Dr. Kohane.

“We think NeoSTX may help patients leave the hospital faster, recover better, and avoid some of the side effects and risks associated with existing pain medications, such as opioids,” said Dr. Berde.

Financial and development investment came from Proteus S.A. and their investors, Boston Children's Hospital's Anesthesia Foundation and Boston Children's Technology Development Fund.

For more on the development of NeoSTX over the past 10 years, please read the following articles:
Safety trial of algal anesthetic kicks off
Could the Secrets that Lie Within Algae Lead to a Long-Acting Local Anesthetic?

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