CURATIVE DESTRUCTION

HOW ALZHEIMER’S DISEASE CAN BE OVERCOME

THE INNOVATOR: DIETER WILLBOLD, ALZHEIMER’S REVOLUTIONIST

Sprind And Prinnovation

Why We Are Committed

Because we want to cure Alzheimer’s dementia. Because we want to relieve the strain on relatives. Because we want to considerably reduce the tremendous costs, and therefore the burden on society. Because we are convinced of the efficacy, tolerability and safety of our active pharmaceutical ingredient (API). Because we want to prove the innovative anti-prionic mechanism of action against self-replicating, toxic, misfolded molecules in patients.

What We Do

Conduct long-term toxicity studies. Prepare a phase II clinical trial to test the efficacy of our innovative API in patients with Alzheimer’s dementia. Carrying out a clinical phase II study on patients with Alzheimer’s dementia. Collect scientific results and make them accessible to the public.

BLOCKBUSTER MARKET POTENTIAL

Alzheimer’s dementia is one of the most care-intensive diseases in the world, causing correspondingly high costs for health care systems. We want to reduce the costs of care for Alzheimer patients. There is a multi-billion market for Alzheimer’s drugs.

PLATFORM VALIDATION

A new anti-prionic mechanism of action is being validated. Upon its success, research on other neurodegenerative diseases of prionic origin can also be initiated.

THE POTENTIAL WE SEE

Halting progression of the disease and curing Alzheimer’s dementia. Enabling aging with dignity. An enormous boost for Germany as a business and science hub. Creating a better world.

Alzheimer’s disease is a plague that destroys brains, lives and human beings. The process of destruction is perfidious and unstoppable, and it all comes down to harmless single proteins in the brain—the Abeta monomers. These proteins aggregate and somehow become toxic. Even worse, the toxic aggregates, the oligomers, replicate themselves at the expense of the monomers and cause more and more neurons in the brain to die. Brain tissue decreases and the patient gradually loses everything that makes them human.

“ONCE THE TOXIC STRUCTURES ARE ELIMINATED, THE DEVASTATING DISEASE CAN BE STOPPED.”

As an expert on structure, function and dysfunction of proteins, Prof. Dr. Dieter Willbold has been observing this dreadful process for a long time with scientific detachment and meticulousness. Most importantly—and this is revolutionary—he is looking at this process in a fundamentally physical and equilibrium reaction-based manner. It is obvious to him where the leverage for a cure needs to be applied. The balance between the beneficial single protein and the toxic aggregate needs to be shifted. According to Willbold, the only way to get this achieved is to administer an active pharmaceutical ingredient that penetrates the brain efficiently and ensures that Abeta monomers are stabilized, and Abeta oligomers are disassembled into harmless monomers.

It is precisely this almost magical active ingredient that Dieter Willbold developed with his research spin-off company Priavoid. PRI-002 is a so-called all-d-peptide that is relatively inexpensive to manufacture. The drug can be administered orally and does not have to be injected intravenously, which is a major benefit to patients. “The active ingredient is important, but the disruptive innovation lies in the mode of action,” Willbold points out. “The process as such is the revolutionary thing, the disassembly of neurotoxic protein aggregates into harmless monomeric building blocks.” He continued, “Once the toxic structures are eliminated, the devastating disease can be stopped.”

The phase I clinical trials with healthy volunteers focusing on safety and tolerability of the active ingredient have already been successfully completed. To further develop the therapeutic agent together with SPRIND, PRInnovation GmbH was founded in August 2021. This SPRIND subsidiary assumes the tasks and duties of the clinical trial’s sponsor. PRInnovation and Priavoid established a research cooperation that now employs approx. 10 team members in order to prove the efficacy of PRI-002 in the next step as part of a clinical phase II study in Alzheimer’s patients. About a year after PRInnovation was founded, the chances have never been better. In 2022, a phase Ib clinical trial with patients suffering from mild cognitive impairment—a precursor to dementia—or mild Alzheimer’s dementia was completed with favorable results. Among others, the study medication was well tolerated and no treatment related side effects were reported. Important insight into the uptake of the active substance could also be obtained. “In particular, a treatment which takes place over a period of years, such as is necessary in the case of Alzheimer’s disease to achieve therapeutic success, requires high tolerability of the active ingredient, good practicability of the administration and a lack of side effects,” explained Prof. Dr. Oliver Peters, who joined the team from the clinical side and provides new momentum as Chief Medical Officer. “The results of the current clinical study with PRI-002 are very encouraging in this context.”

It is important to the Head of the Memory Consultation and the Centre for Dementia Prevention at Berlin’s Charité Hospital, who has been researching Alzheimer’s for over 20 years, that the treatment is practicable in the context of other diseases and the required concomitant medication. “Due to the usually advanced age of our patients, we need to assume that they are already taking several other medications, such as antihypertensive medicines and blood thinners. It is important that interactions between the different medications are avoided. In this respect, we’re extremely optimistic about the PRI-002 mode of action.”

However, long-term toxicology is the biggest milestone still to be achieved before the initiation of the phase II longterm clinical study with afflicted patients. The complex safety testing already started in spring 2021, and studies are still ongoing. If everything goes well, phase II can be applied for, ideally starting in late summer 2023. The study will be carried out as a multicentric trial with the participation of about 30 hospitals in Germany and elsewhere in Europe. “We should not expect a miracle in terms of being finished more quickly all of a sudden. New obstacles can arise every day that may delay our plans— especially considering the fact that we are acting in an extremely dynamic and competitive environment,” remarked Dieter Willbold. “But so far everything is going according to plan.”

BACKGROUND:

Dieter Willbold is a professor of Physical Biology at Heinrich-Heine University in Düsseldorf, Germany, and Director of the Institute for Structural Biochemistry at the Jülich Research Center. Of course, he does not conduct his research on his own, but as a member of a network of highly competent colleagues and scientist friends. Biophysicist and prion researcher Prof. Dr. Detlev Riesner encouraged him to create his company, PRIAVOID. “Willbold, that is a great idea. Now you have to get going and set it up.” Riesner is co-founder of several biotech companies, including the QIAGEN diagnostic company. He has a long-standing friendship with Prof. Dr. Stanley Prusiner , who received the Nobel Prize in Medicine in 1997 for the discovery that there are pathogens that are not composed of DNA and RNA—but only proteins. He named them PRION. The PRI-002 anti-prionic mode of action inspired Dieter Willbold to name his spinoff PRIAVOID. PRIAVOID transfers the anti-prionic MoA of PRI-002 to other diseases that are based on misfolded proteins such as Parkinson’s disease.