More than 250 biotech investors, industry members and investigators gathered online on June 22, 2021 for the third-annual Biotech by the Lake Investor Summit hosted by Northwestern University’s Chemistry of Life Processes Institute (CLP), Oppenheimer & Co., and BioCentury, Inc. The half-day program, moderated by CLP Interim Director Neil Kelleher, featured presentations and lively discussions about neurological disorder breakthroughs, trends, and financing and investment opportunities.

CLP faculty members Hande Ozdinler (Neurology), William Klein (Neurobiology), Yevgenia Kozorovitskiy (Neurobiology), and Richard B. Silverman (Chemistry, Molecular Biosciences, and Pharmacology) kicked off the program with presentations about their translational work targeting neurological disorders.

“We lower the barriers to discovery and catalyze the early-stage chasm that many of us know about in this business and, with our colleagues at Feinberg School of Medicine, we bring innovations from the lab to society,” said Kelleher about CLP’s research mission.

Diagnosing Upper Motor Neuron Diseases

Ozdinler outlined her ideas for improving the success rate of clinical trials using proteomics in the first presentation of the day.

“Our lab focuses on upper motor neurons. These neurons are exceptionally important because they initiate and modulate movement,” says Ozdinler. “Previously, they didn’t think upper motor neurons were therapeutic targets for intervention. Now, we realize that the disease actually starts in the brain.”

Ozdinler’s lab is working with Northwestern Proteomics to develop the first diagnostic tool for upper motor neuron (UMN) diseases using biomarkers to pinpoint the underlying mechanisms behind the disease. Her approach will help clinicians determine and the timing and extent of upper motor neuron loss in patients with ALS, HSP, PLS as well as spinal cord injury and improve success rates of clinical trials.

Breakthrough Alzheimer’s Therapy

Next generation Alzheimer’s disease (AD) immunotherapies were the topic of the next presentation given by Klein. The investigator explained his hypothesis that memory dysfunction during early-stage AD and severe cellular degeneration and dementia during end stage is caused by toxic amyloid-β oligomers, instead of amyloid plaques. It’s a timely topic with the FDA’s recently approval of Aduhelm (aducanumab), the first new therapy approved for AD since 2003.

In April 2021, a new drug, ACU193, that builds on Klein’s hypothesis and targets Aβ oligomers, received Investigational New Drug designation by the Food and Drug Administration. Northwestern spin out Acumen Pharmaceuticals began clinical trials this month.

“Alzheimer’s disease is going to be a tremendous problem the near future, estimated to be a trillion dollars a year in 2015,” said Klein. “I believe the new Aβ oligomer antibodies such as Acumen’s, or perhaps others, may help avert this crisis.”

Inducing Neuroplasticity

Kozorovitskiy’s presentation, “Developing high precision screens for pharmacological traction of neuroplasticity,” informed attendees about exciting new assays that her team has developed that can induce the formation of new dendritic spines in the brain.

“Overlaid on the electronic-like fastener transmission circuits of the brain is a rich array of different kinds of neuro modulators that have been linked to many neurodevelopmental, neurodegenerative and mental health disorders,” Kozorovitskiy said. “Neurons are discrete cells that sometimes have really complex dendritic structure at other times very simple and aspects of the structure and connectivity is enormously important to determining how they function.”

Kozorovitskiy’s assays provide a powerful new way to study how different kinds of molecules alter the potential for plasticity in neurons and to test various drug therapies.

New Treatment for Upper Motor Neuron Diseases

Silverman discussed his lab’s development of a potential new drug called NU-9 for treating upper motor neuron diseases, specifically amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and hereditary spastic paraplegia (HSP).

“10 to 15% of ALS is hereditary and a quarter of the hereditary disease comes from mutations in an enzyme called superoxide dismutase 1, or SOD1,” says Silverman.  “Mutation in SOD1 forms aggregates, and they then accumulate in the neurons and cause neurodegeneration.”

Studies of the orally administered therapy found that NU-9 maintains the health of upper motor neurons in mice with mutant SOD1, as well as those with TAR DNA-Binding Protein 43 kDa (TDP-43), a toxic protein linked to both familiar and sporadic forms of ALS. Silverman’s team is currently engaging in IND-enabling studies for toxicology and safety pharmacology that the researcher estimates could take 18-24 months before possible FDA approval of NU-9 as an Investigational New Drug, for use in clinical trials

Hot Topics in Neurological Disease Therapies and Technologies

Following the Northwestern faculty presentations, BioCentury’s Lauren Martz led a lively discussion with Panelists Ginger S. Johnson, Chief Executive Officer, Cello Health BioConsulting; Norbert Riedel, Chief Executive Officer, Aptinyx Inc.; and Myung Shin, Executive Director and Head of Early Discovery Genetics, Genetics and Pharmacogenomics and member of CLP’s Executive Advisory Board, about the FDA’s recent approval of Biogen’s Aduhelm (aducanumab) for AD and its implications for other for central nervous system disorder biotech companies.

“There are roughly 35 million patients in the world who have this disease [AD], and we really are in need of therapies,” said Bhagat. “It’s great, on the one hand, that the FDA is working with the industry to be able to create biomarkers to be able to get these drugs approved so that there is something for these patients. I think the challenge is, the verdict is still out whether levels of amyloid plaque are correlated to disease at all.”

The panel also weighed in on precision medicine approaches and other areas of unmet need for CNS therapies.

“I have high hopes that CNS is now more ready for prime time,” said Riedel. “I look at our own pipeline at Aptinyx and at the results we have in several phase two clinical trials in chronic pain and in PTSD, as well as a study in non-human primates in Parkinson’s disease.  I think there’s a lot of promising activity that, hopefully, we can take all the way to the finish line to make a difference to patients that are in desperate need for truly effective and efficacious therapies.”

Neuroscience Advances in the Private Sector

The program included presentations by Sean M. Smith, Executive Director of Neuroscience Discovery at Merck & Co., and Casper Hoogenraad, Vice President, Head of Neuroscience Research at Genentech, who discussed their respective company’s approach to drug discovery and development of novel CNS therapies.

“if you look at 2020, neuroscience was only second to oncology for approvals in the FDA, so I do think we’re starting to see some success in the area of neuroscience research,” said Smith. “The reason for this is driven by the growing aging population and the ineffectiveness of current interventions.”

Neurodegeneration, neuroimmunology, and diseases related to aging are Merck’s main focus areas. Having faced many challenges with translation using animal models, explained Smith, Merck changed their approach to focus more on using human biology—information from familial mutations or from genome-wide association studies—to select the best drug targets.

Hoogenraad’s talk began with some sobering statistics. “There are more than 600 neurological diseases, 700 million cases of these disorders reported globally each year, and approximately $800 billion in the US alone spent on health care costs,” he said.

Genentech currently has 14 neuroscience drug candidates across five areas of CNS research, including AD, ALS, frontotemporal degeneration, multiple sclerosis, and progressive supranuclear palsy.

Financing and Investing in Neurological Science Biotech

Oppenheimer research analyst, Jay Olson, led a “lightening round” discussion with distinguished experts on financing and investing in biotechnology companies focused on CNS.  The panel featured Jamil M. Beg, Partner, 5AM Ventures’ Margarita Chavez, Managing Director, AbbVie Ventures, Michael Margolis, Managing Director, Oppenheimer & Co. and Jingwen Wang, Portfolio Manager, Verition Fund Management, LLC.

Panelist enthusiasm for financing and investing in AD drug development in the wake of FDA approval of aducanumab varied from no change in research or investment strategy to a reason for cautious optimism (Margolis). The importance of novel targets that could be validated with biomarkers and platform expertise to support an investment in neurodegeneration was an opinion shared by all.

Panelists also weighed in with advice for early-stage investors and entrepreneurs looking to raise capital for neuroscience ventures.

“We’re coming off one of the best biotech markets in our history,” said Margolis. “But I think times will change. Companies have to be focused and prudent how they spend shareholder money.  Going forward as companies move towards the public markets, there will only be a finite amount of capital available for drug development and eventually commercialization.   As a result, management will need to put their best foot forward and have credible strategic plans to maximize company value.”

Read the ‘Biotech by the Lake 2021’ event program.

Watch the recording of ‘Biotech by the Lake 2021’

Read Oppenheimer’s Report on the program.

by Lisa La Vallee