Dr. Leen Kawas, co-founder and managing general partner at Propel Bio Partners, discusses innovations within the Alzheimer’s care space.
As 21st-century technology leads to medical breakthroughs and new drug treatments, the rising incidence of Alzheimer’s is increasingly becoming one of the biggest challenges to our society and economy. According to the Alzheimer’s Association’s 2023 figures, over six million Americans are currently impacted by this debilitating disease. By 2050, almost 13 million people are predicted to be living with Alzheimer’s.
Alzheimer’s is a disease that impacts not only the patients but caregivers, partners, children, and the whole family as a unit. Alzheimer’s is one of the most expensive diseases we are tackling. In addition to the direct cost of taking care of the patient, the indirect cost is significant and can’t be ignored.
For perspective, approximately one of every three older adults passes away from Alzheimer’s or another form of dementia. Individuals 65 and older survive four to eight years after an Alzheimer’s diagnosis, on average.
This uncertain disease progression brings the need for treatment advances to the forefront.
Overview of the Current Alzheimer’s Landscape
Leen Kawas, Ph.D. is Propel Bio Partners’ Managing General Partner and an accomplished scientist, entrepreneur, and biotech executive. Dr. Kawas, who was previously Athira Pharma’s CEO, has received industry recognition for her drug development work.
Dr. Leen Kawas is also well acquainted with Alzheimer’s, as her grandmother was impacted by the disease. Watching her family member’s painful deterioration spurred Dr. Kawas to choose a career in which she could pursue Alzheimer’s treatments.
In her Propel Bio Partners position, Dr. Kawas evaluates emerging bioscience companies that aim to support companies advance their product and realize their mission.
Dr. Leen Kawas Details Alzheimer’s Financial and Social Impacts
Because of Alzheimer’s substantial care costs, often over an extended period, this disease places a heavy burden on the healthcare system. Dr. Leen Kawas spoke about the financial costs of Alzheimer’s care.
“Alzheimer’s disease is the most expensive disease in our systems. It is costing us over $300 billion in direct and indirect costs. Of course, there are multiple types of dementias, but it’s a really expensive disease,” Dr. Kawas said.
She also offered insights on the impact of an Alzheimer’s diagnosis on the patient’s family. “We don’t think about the indirect cost. Once a family is impacted by Alzheimer’s, it’s not only the patients, but also the caregiver giving up their job to start caring for Alzheimer’s for their family members.
“There’s a significant indirect cost on our society. That’s why I say Alzheimer’s is never a single-person disease. It’s a unit. It’s either the patient and their caregiver or multiple people that are impacted by the disease,” Dr. Kawas remarked.
Not surprisingly, Dr. Leen Kawas noted that many physicians choose not to diagnose an Alzheimer’s patient. With few therapies currently available or accessible, the physician wants to postpone telling the patient (and their family) for as long as possible.
Alzheimer’s is a Highly Complex Disorder
Contrary to the public perception, Alzheimer’s isn’t a well-defined disorder such as diabetes or hypertension. Dr. Leen Kawas explains how each Alzheimer’s patient can have a distinctive disease makeup.
“Alzheimer’s is as complex, if not more complex, than cancer or oncology. There are different genotypes and phenotypes, there are different levels of protein accumulations in the central nervous system, and the different regions of the brain that are being impacted. There’s cardiovascular impact, the ApoeE genotypes that can impact disease progression” Dr. Kawas noted.
She also explained that Alzheimer’s can present itself differently depending on the patient’s career and personal life. “Alzheimer’s presents itself for someone who is, let’s say, a NASA scientist, very differently than someone who uses different domains in their brain, in their career and day-to-day activity.
“The disease and the way that the patient will progress will be very, very different. This makes the way to test for improvement in clinical studies much more challenging than cancer. With cancer, the endpoints, most of the time, are quantitative. The tumor size, cell count. It’s much easier to quantify compared to recovery in the cognitive network,” Dr. Kawas emphasized.
Discrepancies in Animal and Human Models
Next, Dr. Leen Kawas emphasized the difficulty of translating animal-focused Alzheimer’s testing models to human behaviors. “Cognitive network, different type of memories. That’s something that animals don’t have or that we are not able to measure.
“So translation is a big challenge here. I always say that for all of these types of mazes that we test in preclinical models, we’re not testing it in the same way for Alzheimer’s patients. So, it’s really hard to translate. Part of the translational challenge is that in humans and clinical testing, there are more variables,” Dr. Kawas explained.
The Challenges of an Alzheimer’s Diagnosis
Historically, physicians have diagnosed Alzheimer’s cases on a post-mortem basis. The clinician may have suspected a patient had the disorder but couldn’t confirm it until they evaluated the post-mortem test results.
However, Dr. Leen Kawas noted that sophisticated imaging techniques now enable physicians to make an Alzheimer’s diagnosis while the patient is alive. However, one major obstacle stands in the way of the widespread adoption of the imaging-based diagnosis method.
“Now, there are a lot of imaging techniques that confirm the beta-amyloid or plaque accumulation in the brain. We’ve had significant advancement in PET imaging, although the problem is it’s not reimbursed. Yet.
“So, that’s another challenge of access to full diagnosis for Alzheimer’s disease. I think right now, with the approval of two drugs, there should be some path toward reimbursement for some of the imaging modalities.
Snapshot of Emerging Alzheimer’s Drug Therapies
Dr. Leen Kawas profiled three emerging Alzheimer’s drug therapies. Each drug targets the Abeta Amyloid protein aggregation in the brain. This pathology is a primary presentation of Alzheimer’s disease.
Dr. Leen Kawas Calls for Decisive Action
In Dr. Leen Kawas’ view, all three drugs initially showed evidence of slight (but consistent) improvement in different cognitive measures. She believes the FDA’s accelerated approval, which requires a subsequent nine-year testing period, was the right move.
Finally, Dr. Leen Kawas called for real-world studies to gather further evidence of each drug’s efficacy. “We have an indication that these drugs work. We need now to think outside of the box. We need to start testing these drugs in the real world.
“There are going to be a lot of academicians who will study these drugs in controlled clinical trials that will give additional data that you cannot have in just a traditional drug development path. These trials can help with a better understanding of the disease, and I think it’s going to open up opportunities for other modalities, other drugs that are in the pipeline for Alzheimer’s,” Dr. Leen Kawas remarked.
Three Challenges of Alzheimer’s Clinical Trials
As Alzheimer’s drug development continues, Dr. Leen Kawas noted that three factors make a drug candidate’s clinical trials especially difficult. Essentially, a lack of defined disease progression and objective measurement criteria are major complicating factors.
Differing Patient Cognitive Decline Progression
“One, cognition is such a big definition. Cognitive decline and dementia in Alzheimer’s disease and other dementia presents in different ways. It depends on the type of cognitive domains that were mostly used during the development of the neuronal network. “
“Different regions in our brain develop differently based on our day-to-day life, the languages that we speak, and the environment, if you’re living in the city versus in the suburbs. So, it, it’s already a very heterogeneous baseline of cognition, and the way that we advance is also very heterogeneous,” Dr. Kawas noted.
Outdated Alzheimer’s Scales
“The second part is the scales that are being used currently in the clinic. A lot of them are very old. You know, when you say cognition, the gold standard right now for how to test for cognition is ADASCog
“I can’t live with the idea that we’re still using tools in the clinic that are older than me when we have all of this advancement in technology and much more advanced understanding of the disease,” Dr. Kawas lamented.
Clinical Operational Challenges
“The third part is execution when you’re testing for cognition. It’s not tangible, it’s not like blood pressure, and it’s not the size of the tumor. These are heavily impacted by the environment.
“If you go through a very stressful experience, let’s say that you’re stuck in traffic for two hours, you get into the clinic. Do you think you’re going to test in the same way when a patient in another clinic walked to the clinic, a five-minute walk in pleasant weather?
“It’s very different. So, there’s also a lot of that co-variance or variability in the environment around testing for cognition and these less-quantitative endpoints are impacted by all of this,” Dr. Kawas emphasized.
Dr. Leen Kawas’ Assessment of New Biotechnology Therapies
As the development of Alzheimer’s therapies continues, Dr. Leen Kawas expressed hope that promising new treatments will become available. “Hopefully, Alzheimer’s is on the path to a breakthrough. To be realistic, none of the drugs that are approved to date are breakthroughs.
“However, with more approvals and more access and more understanding of the different types of diseases, I think there will be a continued increase in acceptance and appreciation of the hard work a lot of people in our industry have done” she predicted.
With the COVID-19 pandemic as an example, Dr. Kawas noted that this unprecedented global event brought researchers and other parties together to find a solution. “I think COVID has had a positive impact on the industry because what we’ve seen is a whole industry coming together to promote innovation. We had multiple vaccines that had helped to manage the pandemic and allowed us to go back to some sort of a new norm.
“I do hope that people go beyond the headlines and go beyond the general reaction and go into the details of things. And they will see that there are a lot of great things that come out of our industries. These include therapies that help cure some types of cancers and deliver vaccines that help give optionality’s for people,” Dr. Kawas remarked.
The Most Exciting New Biotechnology Therapies
Dr. Leen Kawas noted that three emerging biotechnology therapies are showing great potential. “I would say cell therapy. We’re looking at a lot of new curative approaches and synthetic biology. Microbiome understanding is also another exciting area that we’ve been looking at.
“The third thing that is really, I think, going to be transformative for our industry is the overlap between the high tech, the traditional technology industry alongside the life science and biotech ─ where we are going to see tremendous innovation in clinical trial testing and data processing and I guess the blockchain of data…new ways that we can develop treatments or tools to help us lead a healthier life,” Dr. Kawas concluded.
About Dr. Leen Kawas
Leen Kawas, Ph.D. is an accomplished bio scientist who serves as Propel Bio Partners’ Managing General Partner. Based in Los Angeles, Dr. Kawas supports emerging biotechnology companies that require venture capital and expert guidance to move forward. She relishes the opportunity to play a key role in bringing biotechnology advancements to light.
Prior to her current role, Dr. Leen Kawas served as the Athira Pharma Chief Executive Officer. In addition to spurring the development of several drug candidates, Dr. Kawas guided Athira through its successful initial public offering. Dr. Kawas won several awards for her exceptional Athira leadership.
To prepare for her biotechnology career, Leen Kawas earned a Pharmacy degree from the University of Jordan in her home country. After her 2008 graduation, she came to the United States to pursue an advanced education. In 2015, she graduated from the Foster School of Business’ Executive Training Program. Taken together, her multifaceted education has provided Dr. Leen Kawas with the foundation to become a leader in the biotechnology arena.