A phase 1 clinical trial of the sigma-2 receptor complex allosteric antagonist CT1812, a novel therapeutic candidate for Alzheimer’s disease

Alzheimer’s & Dementia: Translational Research & Clinical Interventions 5 (2019) 20-26


Michael Grundmana, Roger Morgan, Jason D. Lickliter, Lon S. Schneider, Steven DeKosky, Nicholas J. Izzo, Robert Guttendorf, Michelle Higgin, Julie Pribyl, Kelsie Mozzoni, Hank Safferstein, Susan M. Catalanog


We would like to congratulate Roger Morgan, MD; for being a co-author on this new publication

Roger is the VP of Medical Affairs at MedSurgPI LLC.  MedSurgPI is a medical consulting group specializing in strategy for product development, medical affairs, medical monitoring, and fractional medical officer services.  For additional information about MedSurgPI services contact gklein@medsurgpi.com

Read the full article

Abstract:

Background: Elayta (CT1812) is a novel allosteric antagonist of the sigma-2 receptor complex that prevents and displaces binding of Ab oligomers to neurons. By stopping a key initiating event in Alzheimer’s disease, this first-in–class drug candidate mitigates downstream synaptotoxicity and restores cognitive function in aged transgenic mouse models of Alzheimer’s disease.

Methods: A phase 1, two-part single and multiple ascending dose study was conducted in 7 and 4 cohorts of healthy human subjects, respectively. In part A, healthy, young subjects (,65 years old) received CT1812 doses ranging from 10 to 1120 mg (6:2 active to placebo [A:P] per cohort). In part B, subjects were administered 280, 560, and 840 mg once daily for 14 days (8:2 A:P per cohort). An elderly cohort, aged 65-75 years, was dosed at 560 mg once daily for 14 days (7:2 A:P). Serum concentrations of CT1812 in part B were measured on day 3 and 14 and cerebrospinal fluid concentrations on day 7 or 9. Cognitive testing was performed in the healthy elderly cohort at baseline and at day 14 of treatment.

Results: Treatment with CT1812 was well tolerated in all cohorts. Adverse events were mild to moderate in severity and included headache and GI tract symptoms. Plasma concentrations of drug were dose proportional across two orders of magnitude with minimal accumulation over 14 days. Cognitive scores in the healthy elderly cohort were similar before and after treatment.

Conclusions: CT1812 was well tolerated with single dose administration up to 1120 mg and with multiple dose administration up to 840 mg and 560 mg in healthy young and healthy elderly subjects, respectively. CT1812 is currently being studied in early phase 2 trials in patients with Alzheimer’s disease.  2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer’s Association. This is an open access article under the CC BY-NC-ND license: http://creativecommons.org/licenses/by-nc-nd/ 4.0/



Neglecting Regulations and Quality System Requirements is Detrimental to your Business

Mark E. Ramser, VP Quality Management, MedSurgPI, LLC; Peter C. Johnson, MD, Principal, MedSurgPI, LLC; Gerald L. Klein, MD, Principal, MedSurgPI, LLC

It’s never too early to start designing and implementing a company’s quality management system (QMS). Initiating the R&D process is not a problem for companies that have a well-defined QMS and a mature understanding of how it should operate. However, without a well-defined, compliant and effective system, this could be the start of potential future quality and regulatory nightmares. Even with a well-defined system in place, significant problems can occur if the organization is lacking the maturity and experience to utilize it properly. Typically, the R&D function is where most people think a product starts. The founders may not have any understanding of regulatory or quality system requirements. They can simply be focused on developing and launching a product, choosing to worry about the regulatory and quality system requirements once they have a product to sell. Unfortunately, by waiting until the product is ready for market, it will be too late. The ISO 13485 standard, 21 CFR Part 820 (FDA Regulations) and MDR (European Medical Device Regulations) require and expect the product development and launch to be performed under controlled processes and systems. Refer to the following links for the above referenced standards and regulations:

  • ISO 13485 (Quality Management System for Medical Devices)

  • 21 CFR Part 820 (FDA Medical Device Regulations)

  • MDR (European Medical Device Regulation)

The notified bodies and regulators expect the following areas to be controlled and managed per their documented standards and regulations:

Mark Ramsey graphic.png

The most critical in early stage product development are:

  • Documented Quality Management System

  • Design Controls (Design History File sub-bullets to prove all these areas are addressed)

    • Design and Development Planning

    • Design Inputs

    • Design Outputs

    • Design Reviews

    • Design Verification and Validation

  • Change Management (design, system, process, supplier, raw material, etc.)

  • Process and Production Control

    • Process

    • Equipment

    • Supplier Selection and Control

Many of these activities need to be initiated from the start of the R&D process and the establishment of a Quality Policy and Quality Process at the proper time falls squarely upon the CEO. Companies cannot generally recreate documentation history at later dates in preparation for an FDA or regulatory body audit. The company is then open to all the risks related to not having required systems during product development. The risks can vary based on the severity of the issue and can range from:

  • A Form 483 may be issued to the firm. Form 483 is the communications method used by the FDA to inform the company’s management of objectionable conditions. This should be followed up with a thorough investigation, root cause analysis and corrective action within 15 days. These are available to the public, but only when specifically requested.

  • Severe issues on Form 483 or a significant number of issues on Form 483 could result in the issuance of a Warning Letter. A Warning Letter is one of the FDA’s principal means of achieving prompt voluntary compliance with the Act. The warning letters are much more significant than a Form 483 and are publicly posted on the FDA website and are easily searchable. This must be followed up with a thorough investigation, root cause analysis and corrective action within 15 days.

  • Additional actions can result in a consent decree, product seizure and up to and including criminal prosecution against the firm and individuals, with a special focus on the CEO.  A consent decree may be viewed as the equivalent to a court order under which the manufacturing and distribution of products can only resume, with conditions closely monitored by FDA.

The regulations defined in 21 CFR Part 820 are legal requirements and carry the stiff penalties noted above. This carries much more significance than merely an ISO standard that defines the requirements without having any legal recourse. One must keep this in mind from the earliest possible point of the inception of the company and not just during the product launch. Not following QMS at product inception and all along the development cycle can have dire consequences for the company.

The timing of onset and the complexity of any company’s QMS is dependent upon the risk that a product may represent when used with humans. Therefore, judgment and expertise are required to properly craft and institute such systems. MedSurgPI can assist your company at the earliest stages to institute a QMS, perform Gap Assessment and Corrective Actions for an existing QMS and assist with the ongoing management of a QMS. Please contact MRamser@medsurgpi.com for additional information.

MedSurgPI welcomes Mark Ramser

MedSurgPI welcomes Mark Ramser as Vice President of Quality Management for Devices.  Mark brings over 25 years of Quality Management experience.  His unique skill set focuses primarily on Quality Assurance, (QA) however, he also has spent considerable time in operations and supply chain.  Mark has extensive experience in medical device quality systems being a former Global Director of QA.

Mark has a BS,  in Mechanical Engineering  from Kettering University (formerly GMI),  and MBA,  in Finance from Case Western Reserve University.  He has also earned a six-sigma black belt as a quality engineer.  Mark has been recognized for strategic planning and program implementation impacting bottom line results through cost reduction, productivity improvements, effective compliance.  So that in addition to QA management Mark is noted for business acumen related to financial, supply chain and operations.

If you wish to consult with Mark, please contact: info@medsurgpi.com or call 919-807-9132

Todd Rowland, MD joins MedSurgPI

MedSurgPI welcomes Dr. Todd Rowland to the MedSurgPI team.  Dr. Rowland has more than 25 years of healthcare industry experience. He brings unique executive experience as a practicing physician, CEO of health information exchange, chief medical information officer, enterprise senior vice president CIO, and principal investigator for several federal grants.

For more information on Dr. Rowland and other associates, visit 'Our Team' portion of the website.

 

$78 million invested as Innovation Works celebrates 20 years

Aethon turned a couple hundred thousand dollars into an international robotics company with delivery robots in hospitals and hotels.

TissueInformatics used a six-figure grant to build a ground-breaking tissue engineering company that raised more than $25 million before a top biotech company bought it.

Both Pittsburgh-area companies were among the first to receive funding from Innovation Works decades ago. And both said that the initial investment led to millions more.

“Without Innovation Works, we probably would not have gotten started as a company,” said Aldo Zini, CEO of Aethon. “It wasn’t just the money, but they also opened some doors for us in order to raise more.”

Innovation Works has been providing early-stage investment to young Pittsburgh startup companies for 20 years. The organization celebrated its anniversary last week by recognizing the achievements of the companies it has helped start and fund.

In its 20 years, Innovation Works, now based in the North Side’s Nova Place, has worked with more than 1,000 companies. Nearly 300 were formed with direct assistance from the organization, and 376 companies received investments totaling $78 million. The companies went on to raise an additional $2.1 billion.

Innovation Works claimed it has created or retained nearly 12,000 jobs, nearly two-thirds of which don’t require an advanced degree. More than half of the companies have a woman founder; 72 percent of the founders came from local universities, and 86 percent of the companies work source from vendors in Pittsburgh, according to information complied by Innovation Works.

“I’m proud of the companies and the entrepreneurs. We have a saying here that we succeed when they succeed. At the end of the day, it’s not about us,” said Rich Lunak, president and CEO of Innovation Works, where he has worked since 2005. “We all take a lot of pride in that.”

The organization calculated that $3.60 was returned to the state economy for every $1 of state money invested. The company receives $3.5 million a year in state money.

Zini said there was a lot of skepticism over robotics companies in the early 2000s, when Aethon was just getting its start. The dot-com bubble had just burst and some investments in robotics in the 1990s didn’t pan out, leaving investors shy.

“Innovation Works, they stepped up,” Zini said.

The organization invested a few hundred thousand in Aethon over a two rounds of investing starting in 2002. Since, Aethon raised more than $50 million. ST Engineering bought Aethon in 2017. The Singapore firm kept the company in the Pittsburgh-area and allowed it to grow.

Aethon has added 18 people to its team over the last 10 months and plans to add another 10, Zini said. The company is moving into a larger building. It has robots in China, Turkey, Singapore, Australia and all over Europe.

But Zini hasn’t forgotten who helped the company at the beginning. He’ll talk to the staff at Innovation Works whenever he is looking for new hires or advice.

“And they’re still helpful,” Zini said.

When four doctors and scientists at University of Pittsburgh spun TissueInformatics in 1997, the startup scene in Pittsburgh was shaky. The city, and its reputation, was still recovering from the collapse of the steel industry, said Dr. Peter Johnson, who came to Pitt in 1987 to train as a plastic surgeon and was one of the three founders of TissueInformatics, which used machine vision to identify pathology slides.

Johnson said building a biotech company in Pittsburgh was rare at that time.

“They took a leap as one of the first to say this was a sector that we really need to invest in,” Johnson said.

TissueInformatics went on to raise $25 million over five years. In 2004, Paradigm Genetics, a North Carolina company, bought the startup. Johnson moved to the Raleigh area where he still lives. He recently bought a 40-acre farm, grows barley and plans to open a distillery.

Innovation Works invited Johnson back to Pittsburgh two years ago to speak. He was impressed the growth of the tech scene. And he expects Innovation Works to keep it growing by finding undiscovered technologies and taking chances, just like it did years ago.

“They’re going to figure out where the fringe is,” Johnson said.

Aaron Aupperlee is a Tribune-Review staff writer. You can contact Aaron at 412-336-8448, aaupperlee@tribweb.com or via Twitter @tinynotebook

UMASS Lowell M2D2 / Advancing Med Device & Biotech Innovations

Thursday, September 13, 2018

DESCRIPTION

Created especially for healthcare startups and medtech innovators: A half-day workshop packed with authoritative insights on leading-edge technologies, new best practices, business intelligence, and networking opportunities (with continental breakfast and light lunch included).

WORKSHOP AGENDA

7:30-8:00 Coffee w/continental breakfast

8:00-8:15 Welcome & Introductions

8:15-9:15 Blockchain & Artificial Intelligence – Real World Healthcare Applications

  • Speakers: Kris Srinivasan, CEO, Life Sciences, Alpha MD & Edward Bukstel, CEO, Clinical Blockchain

9:15-9:45 Blockchain: What Startups need to succeed; What larger corporations like J&J can do to support their growth

  • Speaker: Kate Merton, Head of JLABS NYC & Boston — J&J Innovation

9:45-10:15 Healthcare Industry Update

  • Speaker: Ibraheem Badejo, Senior Director, New Ventures, J&J Innovation

10:15-10:30 Break

10:30-11:00 Continuum of Medical Affairs in a Startup Company

  • Speakers: Dr. Peter Johnson & Dr. Gerald Klein, Co-Principals, MedSurgPl, LLC

11:00-11:30 Friction Points in Health Communications at Point of Care

  • Speaker: Richard Nordstrom, CEO, Liberate Ideas, Inc.

11:30-12:00 Lunch Break

12:00-12:45 Mock interview with Investors: One or more investors with successfully financed entrepreneur and startup pitch. How to deal with Investors.

  • Speakers: Steven Schwartz, Robert Bausmith

12:45-1:00 Ice Cream Hour: One-on-one interactive meetings with the speakers and the management of JLabs while you enjoy ice-cream during Q&A.

  • You are welcome to send in your questions in advance via email to Kris@AlphaMD.com or ask during Ice Cream Hour.  You will also be able to talk in person with Kate Merton, Head of JLABS NYC & Boston, and Dr. Ibraheem Badejo, Senior Director, New Ventures, J&J Innovation.

 

MedSurgPI: Physician Functional Service Provider

GERALD L. KLEIN, MD; PETER C. JOHNSON, MD; ROGER MORGAN, MD

     MedSurgPI is the preeminent Physician Functional Service Provider.  We provide medical strategy, medical monitoring, medical affairs, and medical writing from our experienced physician team of seasoned executives.  Our goal is to provide this outsourced service to increase efficiencies and decrease cost for drug, device, diagnostic, and nutritional development services.

     MedSurgPI doctors are flexible and can provide short term assistance or long term collaboration. 

     Whether you want a medical strategy, clinical trial guidance, medical monitor or an interim Chief Medical Officer, contact MedSurgPI, LLC at:  http://www.medsurgpi.com/contact-1/

James D. Hundley, M.D. of MedSurgPI co-authors book: My Hip Hurts!

James D. Hundley, M.D., Physician Associate with MedSurgPI, LLC has co-authored a book My Hip Hurts!: Causes and Treatment of Hip Pain in Seniors.  Authors Dr. Hundley and Richard J. Nasca, M.D. are two orthopaedic surgeons with over 100 combined years of training and experience.  This is an exciting book as Drs. Hundley and Nasca describe conditions of the hip suffered by older people, what can be done for them, and what they would recommend.  Simple drawings and x-rays are used for illustration along with a glossary to help understand medical terms.

This book is available through Amazon at the following link:  My Hip Hurts!: Causes and Treatment of Hip Pain in Seniors 

AlphaMD and MedSurgPI have entered into a partnership to provide comprehensive Product Development and Commercialization with Medical Affairs Services to clients worldwide.

This service is a proprietary process to assist start-ups and established Life Science companies launch their drug, diagnostic and medical device products successfully from concept through launch and post-market surveillance. It encompasses proof-of-concept studies, clinical trial assistance, market research, product development, health economics and outcomes research services, a successful launch, data analytics and pharmacovigilance.