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Cassava Sciences (SAVA): Let’s Shed Some Light on That Crash

Cassava Sciences (SAVA): Let’s Shed Some Light on That Crash

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Investing in micro-cap biotechs is a risky business. 

Although 2020 has seen a host of small biotech companies’ valuations soar on the back of promising trial data for a COVID-19 vaccine or treatment, it’s easy to forget just how devastating negative results can be. Bring results of a failed clinical trial to the public‘s attention, and the stock gets dropped faster than you can say “primary endpoint.”

Case in point: Cassava Sciences (SAVA). The Austin, Texas-based company shed 74% of its value in Friday’s session following the release of disappointing results from a Phase 2 study evaluating Cassava's lead investigational drug, PTI-125, in Alzheimer's disease (AD).

The candidate failed to meet the primary endpoint, which was to produce a meaningful improvement in a number of AD biomarkers, when compared to the placebo.

Targeting an altered form of filamin A, a scaffolding protein present in the body, PTI-125 is a small molecule designed to reduce the protein’s effects. Present in the brains of AD patients, the extremely toxic form of the protein interferes with the normal function of neurons, thereby, causing neuroinflammation and neurodegeneration.

The company has noted that the high variability in biomarkers may have masked the drug’s effect, with it planning to further analyze the data.

Although Maxim's Jason McCarthy notes there were positives to take away from the data, they are not enough to dissuade the analyst from changing his model for Cassava.

McCarthy said, “The data failed to meet the primary endpoint of significant improvement in AD biomarkers from baseline to Day 28 in treatment groups compared to placebo. A significant reduction in CSF levels, however, was noted in neuroinflammation biomarker IL1-beta, a secondary endpoint (p<0.035). Nonetheless, a miss is a miss and the path forward for PTI-125 is unclear.”

Accordingly, the analyst downgraded SAVA to Hold and removed the previous $12 price target “while the company further evaluates the data and path forward.” (To watch McCarthy’s track record, click here)

Only one other analyst has reviewed Cassava over the past three months, assigning the stock a Hold rating. Therefore, the micro-cap biotech has a Hold consensus rating.

To find good ideas for stocks trading at attractive valuations, visit TipRanks’ Best Stocks to Buy, a newly launched tool that unites all of TipRanks’ equity insights.

The post Cassava Sciences (SAVA): Let’s Shed Some Light on That Crash appeared first on TipRanks Financial Blog.

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Spread & Containment

SoCal Industrial Prioritizes Speed, Power and Sustainability 

Movement is key in the SoCal industrial space. Industrial real estate occupies some 200 million square feet of space in the SoCal region, with much of…

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Movement is key in the SoCal industrial space. Industrial real estate occupies some 200 million square feet of space in the SoCal region, with much of the activity driven by the Ports of L.A. and Long Beach. The swift movement – not storage – of goods from the port to their destinations, is priority. Currently, the industrial vacancy rate sits at 4%. While the increase in e-commerce during the COVID-19 pandemic caused industrial volume in the region to surge, volumes have declined 30% over the past year, returning to more normal, though still high, levels comparable to 2019.  

Attendees of I.CON West in Long Beach, California, had the opportunity to visit three impressive industrial properties in the SoCal region. The projects by Goodman, Watson Land Company and Bridge Industrial are in three different phases of completion and range in size from 165,000-500,000 square feet. 

The I.CON West group toured a 90-acre site in Long Beach purchased by Goodman, a globally traded real estate company, five years ago. The Goodman Commerce Center Long Beach was previously a Boeing manufacturing center with 100-foot clear heights that made it well suited for the current tenant Relativity, a company that makes 3-D printed rockets.  

Power is a major consideration for tenants in the region. Tenants are also asking for clear heights that are increasingly taller; the typical height in 2012 was closer to 32 feet, but buildings in the area are inching closer to the 40-foot range.  

Environmental concerns are top of mind in California. Long Beach requires a methane mitigation system and Boeing also required a vapor barrier to be added to the site as part of their land use covenant. The area was previously heavily comprised of oil fields, so vapor barriers are common. The state is working toward a 2035 goal of having 100% of new cars and light trucks sold in California be zero-emission vehicles, so sites are considering the current usage and future expansion of EV charging stations. Goodman’s site is equipped with 26 EV-charging stations but has the capability to expand to 100 more, as needs require. 

Watson Land Company’s site in Carson, California, is located in the South Bay, an area that includes many 1980s-era Class B buildings that are being redeveloped to meet modern usage and demand.  

One of the main challenges faced in this area is the heavy clay soil; Watson had to install an underground storm drain system to allow for percolation.  

One of the main advantages of the area is that it’s within the “Overweight Container Corridor” that allows for heavier vehicles – up to 95,000 pounds – to pass through with containers from the port.  

Watson Land Company is pursuing U.S. Green Building Council LEED Gold certification for this site; they were able to reuse or recycle 98.6% of the material crushed from the previous buildings. The company aims for LEED Silver or Gold in many of their buildings in California, part of its early legacy dating to the founding of Watson Land Company in 1912 with a commitment to serve as “good stewards of the land.” 

Another feature of the Watson Land Company’s building: ample skylights – a 3% skylight to roof ratio – and clerestory windows to bring in maximum natural light. 

For the final stop of the tour, attendees visited a former brownfield site in Torrance, California, developed by Bridge Industrial. Bridge Industrial considers their team problem solvers who can tackle sites like this one that require significant remediation. They have transformed the brownfield site into a modern, airy industrial facility with two stories of office space.  

Power, again, came up as a critical concern for tenants. Bridge Industrial used to provide 2,000 amps as the standard but now provides 4,000 amps as the new standard in response to tenant needs. One of Bridge Industrial’s buildings in Rancho Cucamonga (roughly a two-hour drive east from Long Beach) offers 4,000 amps with provisions for additional future service up to an astonishing 8,000 amps.   

With the dual ports and the LAX airport nearby, SoCal is poised to continue its strong industrial presence. Port activity, environmental regulations and evolving tenant demands – including for increasing power capabilities – are critical considerations for developers, owners and investors operating in this bustling region.


This post is brought to you by JLL, the social media and conference blog sponsor of NAIOP’s I.CON West 2024. Learn more about JLL at www.us.jll.com or www.jll.ca.

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Chronic stress and inflammation linked to societal and environmental impacts in new study

From anxiety about the state of the world to ongoing waves of Covid-19, the stresses we face can seem relentless and even overwhelming. Worse, these stressors…

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From anxiety about the state of the world to ongoing waves of Covid-19, the stresses we face can seem relentless and even overwhelming. Worse, these stressors can cause chronic inflammation in our bodies. Chronic inflammation is linked to serious conditions such as cardiovascular disease and cancer – and may also affect our thinking and behavior.   

Credit: Image: Vodovotz et al/Frontiers

From anxiety about the state of the world to ongoing waves of Covid-19, the stresses we face can seem relentless and even overwhelming. Worse, these stressors can cause chronic inflammation in our bodies. Chronic inflammation is linked to serious conditions such as cardiovascular disease and cancer – and may also affect our thinking and behavior.   

A new hypothesis published in Frontiers in Science suggests the negative impacts may extend far further.   

“We propose that stress, inflammation, and consequently impaired cognition in individuals can scale up to communities and populations,” explained lead author Prof Yoram Vodovotz of the University of Pittsburgh, USA.

“This could affect the decision-making and behavior of entire societies, impair our cognitive ability to address complex issues like climate change, social unrest, and infectious disease – and ultimately lead to a self-sustaining cycle of societal dysfunction and environmental degradation,” he added.

Bodily inflammation ‘mapped’ in the brain  

One central premise to the hypothesis is an association between chronic inflammation and cognitive dysfunction.  

“The cause of this well-known phenomenon is not currently known,” said Vodovotz. “We propose a mechanism, which we call the ‘central inflammation map’.”    

The authors’ novel idea is that the brain creates its own copy of bodily inflammation. Normally, this inflammation map allows the brain to manage the inflammatory response and promote healing.   

When inflammation is high or chronic, however, the response goes awry and can damage healthy tissues and organs. The authors suggest the inflammation map could similarly harm the brain and impair cognition, emotion, and behavior.   

Accelerated spread of stress and inflammation online   

A second premise is the spread of chronic inflammation from individuals to populations.  

“While inflammation is not contagious per se, it could still spread via the transmission of stress among people,” explained Vodovotz.   

The authors further suggest that stress is being transmitted faster than ever before, through social media and other digital communications.  

“People are constantly bombarded with high levels of distressing information, be it the news, negative online comments, or a feeling of inadequacy when viewing social media feeds,” said Vodovotz. “We hypothesize that this new dimension of human experience, from which it is difficult to escape, is driving stress, chronic inflammation, and cognitive impairment across global societies.”   

Inflammation as a driver of social and planetary disruption  

These ideas shift our view of inflammation as a biological process restricted to an individual. Instead, the authors see it as a multiscale process linking molecular, cellular, and physiological interactions in each of us to altered decision-making and behavior in populations – and ultimately to large-scale societal and environmental impacts.  

“Stress-impaired judgment could explain the chaotic and counter-intuitive responses of large parts of the global population to stressful events such as climate change and the Covid-19 pandemic,” explained Vodovotz.  

“An inability to address these and other stressors may propagate a self-fulfilling sense of pervasive danger, causing further stress, inflammation, and impaired cognition in a runaway, positive feedback loop,” he added.  

The fact that current levels of global stress have not led to widespread societal disorder could indicate an equally strong stabilizing effect from “controllers” such as trust in laws, science, and multinational organizations like the United Nations.   

“However, societal norms and institutions are increasingly being questioned, at times rightly so as relics of a foregone era,” said Prof Paul Verschure of Radboud University, the Netherlands, and a co-author of the article. “The challenge today is how we can ward off a new adversarial era of instability due to global stress caused by a multi-scale combination of geopolitical fragmentation, conflicts, and ecological collapse amplified by existential angst, cognitive overload, and runaway disinformation.”    

Reducing social media exposure as part of the solution  

The authors developed a mathematical model to test their ideas and explore ways to reduce stress and build resilience.  

“Preliminary results highlight the need for interventions at multiple levels and scales,” commented co-author Prof Julia Arciero of Indiana University, USA.  

“While anti-inflammatory drugs are sometimes used to treat medical conditions associated with inflammation, we do not believe these are the whole answer for individuals,” said Dr David Katz, co-author and a specialist in preventive and lifestyle medicine based in the US. “Lifestyle changes such as healthy nutrition, exercise, and reducing exposure to stressful online content could also be important.”  

“The dawning new era of precision and personalized therapeutics could also offer enormous potential,” he added.  

At the societal level, the authors suggest creating calm public spaces and providing education on the norms and institutions that keep our societies stable and functioning.  

“While our ‘inflammation map’ hypothesis and corresponding mathematical model are a start, a coordinated and interdisciplinary research effort is needed to define interventions that would improve the lives of individuals and the resilience of communities to stress. We hope our article stimulates scientists around the world to take up this challenge,” Vodovotz concluded.  

The article is part of the Frontiers in Science multimedia article hub ‘A multiscale map of inflammatory stress’. The hub features a video, an explainer, a version of the article written for kids, and an editorial, viewpoints, and policy outlook from other eminent experts: Prof David Almeida (Penn State University, USA), Prof Pietro Ghezzi (University of Urbino Carlo Bo, Italy), and Dr Ioannis P Androulakis (Rutgers, The State University of New Jersey, USA). 


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Acadia’s Nuplazid fails PhIII study due to higher-than-expected placebo effect

After years of trying to expand the market territory for Nuplazid, Acadia Pharmaceuticals might have hit a dead end, with a Phase III fail in schizophrenia…

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After years of trying to expand the market territory for Nuplazid, Acadia Pharmaceuticals might have hit a dead end, with a Phase III fail in schizophrenia due to the placebo arm performing better than expected.

Steve Davis

“We will continue to analyze these data with our scientific advisors, but we do not intend to conduct any further clinical trials with pimavanserin,” CEO Steve Davis said in a Monday press release. Acadia’s stock $ACAD dropped by 17.41% before the market opened Tuesday.

Pimavanserin, a serotonin inverse agonist and also a 5-HT2A receptor antagonist, is already in the market with the brand name Nuplazid for Parkinson’s disease psychosis. Efforts to expand into other indications such as Alzheimer’s-related psychosis and major depression have been unsuccessful, and previous trials in schizophrenia have yielded mixed data at best. Its February presentation does not list other pimavanserin studies in progress.

The Phase III ADVANCE-2 trial investigated 34 mg pimavanserin versus placebo in 454 patients who have negative symptoms of schizophrenia. The study used the negative symptom assessment-16 (NSA-16) total score as a primary endpoint and followed participants up to week 26. Study participants have control of positive symptoms due to antipsychotic therapies.

The company said that the change from baseline in this measure for the treatment arm was similar between the Phase II ADVANCE-1 study and ADVANCE-2 at -11.6 and -11.8, respectively. However, the placebo was higher in ADVANCE-2 at -11.1, when this was -8.5 in ADVANCE-1. The p-value in ADVANCE-2 was 0.4825.

In July last year, another Phase III schizophrenia trial — by Sumitomo and Otsuka — also reported negative results due to what the company noted as Covid-19 induced placebo effect.

According to Mizuho Securities analysts, ADVANCE-2 data were disappointing considering the company applied what it learned from ADVANCE-1, such as recruiting patients outside the US to alleviate a high placebo effect. The Phase III recruited participants in Argentina and Europe.

Analysts at Cowen added that the placebo effect has been a “notorious headwind” in US-based trials, which appears to “now extend” to ex-US studies. But they also noted ADVANCE-1 reported a “modest effect” from the drug anyway.

Nonetheless, pimavanserin’s safety profile in the late-stage study “was consistent with previous clinical trials,” with the drug having an adverse event rate of 30.4% versus 40.3% with placebo, the company said. Back in 2018, even with the FDA approval for Parkinson’s psychosis, there was an intense spotlight on Nuplazid’s safety profile.

Acadia previously aimed to get Nuplazid approved for Alzheimer’s-related psychosis but had many hurdles. The drug faced an adcomm in June 2022 that voted 9-3 noting that the drug is unlikely to be effective in this setting, culminating in a CRL a few months later.

As for the company’s next R&D milestones, Mizuho analysts said it won’t be anytime soon: There is the Phase III study for ACP-101 in Prader-Willi syndrome with data expected late next year and a Phase II trial for ACP-204 in Alzheimer’s disease psychosis with results anticipated in 2026.

Acadia collected $549.2 million in full-year 2023 revenues for Nuplazid, with $143.9 million in the fourth quarter.

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