How To Innovate In Your Trading

Very little has been written in trading psychology about innovation.  And yet, wherever I've encountered traders and portfolio managers with longstanding track records of success, I've seen evidence of innovation.  The innovator is the one who asks really good questions, really original questions.  The innovator is the one who sees changes in market behavior and wants to figure out what that's all about and how to take advantage of it.  

When we become completely P/L focused, there's little bandwidth left for innovation.  Superior trading requires an absorption in markets; superior good idea generation requires getting away from screens and seeing a bigger picture.

On a recent trip to Nashville, I had plenty of time away from screens and started asking simple questions, but questions I hadn't asked before.  For instance, I wondered if the best predictors of what happens in a given equity market index (such as SPX) might come from stocks outside that index (such as Russell 2000) or subsets of that index (such as the Dow).  In other words, do certain groups of stocks tend to lead momentum moves, trending moves, or reversal moves in a given index?  Oddly enough, I had always looked for data generated by an index to anticipate moves in that index.  But what if that's just playing the same game as everyone else?

Early days and we'll see what the research brings, but it's promising so far.  For example, it turns out that strength in the average RSI of small cap stocks is strongly correlated with future short-term strength in the SPX, accounting for almost all of the gains in SPY for the past two years.  Who knew?

But the great psychological benefit of innovation is that it leads to curiosity and discovery and fascination.  It rekindles our interest in markets when we could otherwise be ground down by choppy trading conditions and lackluster P/L.  Finding a new edge feels like becoming a new trader all over again, with all the new enthusiasm and excitement.  Come to think of it, that's also what leads to keeping relationships new and that's what leads to keeping life fresh and interesting.  When we innovate, look at new things, try new things, and learn new things, we are reborn--and that *gives* us energy.

http://traderfeed.blogspot.com/2021/06/how-to-innovate-in-your-trading.html

 

China-partnered oncology biotech Ambrx Biopharma refiles for a $100M IPO

 Ambrx Biopharma, a Phase 2/3 oncology biotech developing engineered antibody-drug conjugates, filed on Friday with the SEC to raise up to $100 million in an initial public offering.

Ambrx Biopharma is developing a novel class of engineered precision biologics using a proprietary genetic code technology platform that allows it to incorporate, in a site-specific manner, synthetic amino acids into proteins within living cells, which the company believes could offer safety and efficacy benefits over conventional conjugation approaches which use natural amino acids. The company's lead candidate, ARX788, is an antibody-drug conjugate currently being studied in breast, gastric and other solid tumors. The most advanced trial of ARX788 is being conducted by Ambrx Biopharma's partner, NovoCodex Biopharmaceuticals, in China in patients with HER2-positive metastatic breast cancer. The ongoing Phase 2/3 trial is expected to report topline data by the end of 2022. 

Ambrx originally set terms to price an IPO in mid-2014, before withdrawing the deal. In 2015, it was acquired by a consortium of Asian pharmaceutical and private equity investors. In late 2020, Ambrx raised $200 million from US crossover investors.

The La Jolla, CA-based company was founded in 2003 and booked $14 million in revenue for the 12 months ended December 31, 2020. It plans to list on the NYSE under the symbol AMAM. Ambrx Biopharma filed confidentially on February 3, 2021. Goldman Sachs, BofA Securities, and Cowen are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: AMAM

https://www.renaissancecapital.com/IPO-Center/News/82215/China-partnered-oncology-biotech-Ambrx-Biopharma-refiles-for-a-$100-million

Diabetes mainstay metformin tamps down lung inflammation in COVID models

 The 27-year-old diabetes drug metformin has been studied for its potential use in a wide range of other disorders, including heart disease and cancer. Now researchers led by the University of California, San Diego, say the diabetes mainstay might help prevent lung inflammation in patients with COVID-19.

The researchers tested metformin in a mouse model of severe lung inflammation that can result from COVID-19—a dangerous condition called acute respiratory distress syndrome (ARDS). The drug inhibited the onset of ARDS and relieved its symptoms, they reported in the journal Immunity.

The researchers discovered that metformin inhibits the activation of the “NLRP3 inflammasome,” which resides in the immune system and causes inflammatory responses. That’s because of the drug’s mechanism of action: It stops the production of an energy-storing molecule in liver cells called ATP, which helps lower glucose.

The new study’s co-author, UCSD pharmacology and pathology professor Michael Karin, Ph.D., had previously discovered a link between ATP and NLRP3 inflammasome activation. They also found that clearing damaged mitochondria—the energy centers inside cells—lowered the activity of the inflammasome and inflammation.

The potential utility of metformin in lung disease has been explored by other research teams. Scientists at the University of Alabama, Birmingham, for example, found that metformin reversed lung fibrosis in mice. The key, they determined, was the drug’s ability to activate AMPK, an enzyme that they believe boosts the metabolism of lung cells, allowing them to resolve fibrosis.

The UCSD researchers tied metformin’s ability to lower inflammation in ARDS to its inhibition of another enzyme, CMPK2. The effect of metformin on ARDS is “extensive,” and likely to be effective at the dose typically prescribed to diabetes patients, the authors wrote in the study.

Several observational studies have reported a link between metformin use and a reduction of mortality risk in patients with COVID-19, the UCSD team noted in the study—a phenomenon they believe their new research helps to explain, they said in a statement.

https://www.fiercebiotech.com/research/diabetes-mainstay-metformin-tamps-down-lung-inflammation-covid-models

Humanigen angling to go from zero to $1B with U.S., U.K. COVID-19 therapy filings

 Humanigen could go from zero to $1 billion in sales if its COVID-19 treatment clears regulatory review in the U.S. and U.K., analysts from Cantor Fitzgerald said.

The self-described “cytokine storm company” filed a rolling submission in the U.K. Monday for authorization of lenzilumab to treat hospitalized COVID-19 patients. This follows a May 28 authorization filing to the FDA.

“We continue to think that [Humaingen]'s COVID-19 opportunity and the rest of its pipeline are underappreciated,” said Cantor’s note. “Despite vaccine uptake, there continues to be a need for proven therapies that are variant-agnostic for patients who remain at risk of COVID-19.”

The therapy could become a standard of care and bring in $1 billion in sales in the first 12 months, the firm estimated. Humanigen currently has no product sales.

Lenzilumab’s submissions are supported by data from a phase 3 clinical trial called LIVE-AIR that found a 54% improvement in the likelihood of survival without ventilation among patients who received the therapy. When paired with corticosteroids and remdesivir, that improvement jumped to 92%. Patients did not suffer any adverse events, and lenzilumab's safety was comparable to placebo.

Humanigen met its goal of filing for FDA authorization by June. The company also wants to get the therapy cleared for a full approval, but the agency is likely to request more trials first.

While several therapies are available for certain COVID-19 patients, the field remains wide open for new ones that can help critically ill people. Virus variants have also put a strain on drug developers, sending Big Pharmas like Eli Lilly back to the drawing board shortly after gaining authorization for a remedy. 

Lenzilumab targets GM-CSF, a cytokine associated with negative outcomes in COVID-19 patients. By neutralizing the cytokine, drug developers including Humanigen and GlaxoSmithKline figure they may be able to counter life-threatening complications that arise when the immune system reacts particularly strongly to the virus.

"Despite vaccine uptake, there continues to be a need for proven therapies that are variant-agnostic for patients that remain at risk of COVID-19," said Humanigen CEO Cameron Durrant. "Now, with applications in the U.S. and in the U.K., we feel we can help tackle this global challenge. We hope to provide a powerful solution for hospitalized patients on both sides of the Atlantic."

Humanigen's therapy is also under development for other conditions that involve cytokine storm, including acute graft-versus-host disease. Lenzilumab hit its primary goal in a phase 3 trial testing its ability to prevent or treat hyperinflammation or cytokine storm. A phase 2 study for the same indication is sponsored by the National Institutes of Health. 

Cytokine storm is an immune system overreaction that can result from an infection, autoimmune condition or disease. Research suggests COVID-19 causes this reaction, kicking the immune system into overdrive in severe cases.

https://www.fiercebiotech.com/biotech/humanigen-angling-to-go-from-zero-to-1b-us-uk-covid-19-therapy-filings

UK study: Pfizer, AstraZeneca vaccines offer protection against Delta variant

 A British study released on Monday found that the Pfizer-BioNTech and AstraZeneca COVID-19 vaccines offer solid protection against hospitalization due to the Delta variant, which recently became the dominant strain in the country. 

Public Health England determined that the full two-dose Pfizer-BioNTech vaccine offers 96 percent protection against hospitalization, and the AstraZeneca vaccine gives 92 percent protection against hospitalization.  

The preprinted analysis concluded that the protection rates are “comparable” to the vaccines’ effectiveness against the Alpha variant.

he analysis involved 14,019 people in England infected with the Delta strain, including 166 who were hospitalized, between April 12 and June 4. 

Public Health England said more research was needed to determine the mortality rate from the Delta variant. 

Mary Ramsay, the head of immunization at Public Health England, said in a release that the “hugely important findings” show the vaccines give “significant protection” against hospitalization from the Delta strain.

“It is absolutely vital to get both doses as soon as they are offered to you, to gain maximum protection against all existing and emerging variants,” she said.

The Delta variant, also known by the scientific name B.1.617.2, was first discovered in India before it spread to at least 74 countries, including the United Kingdom, where it overtook the Alpha variant to become the dominant strain. 

Another analysis in Scotland published as a letter Monday in the Lancet medical journal concluded that the vaccines were slightly less effective against infection with the Delta strain than other variants. But protection against serious illness was similar to other strains in the analysis of 19,543 cases. 

The Pfizer-BioNTech vaccine was found to give 92 percent protection against the Alpha strain and 79 percent against the Delta variant. The analysis determined the AstraZeneca vaccine was 73 percent effective against Alpha and 60 percent against Delta, after both doses.

The studies were released as concerns have mounted about the Delta variant as it spreads.

An earlier preprint study from Public Health England found that two doses of Pfizer-BioNTech or AstraZeneca were 88 percent and 60 percent effective against symptomatic Delta cases, respectively. But the vaccines gave 33 percent protection to partially vaccinated people with both vaccines. 

British Prime Minister Boris Johnson declared that the planned relaxation of coronavirus restrictions for June 21 would be pushed back up to four weeks as the U.K. sees growing Delta cases.

President Biden’s chief medical adviser Anthony Fauci said last week that more than 6 percent of sequenced U.S. COVID-19 infections were from the Delta variant. He also warned that it was “essentially taking over” the U.K.

https://thehill.com/policy/healthcare/558339-uk-study-pfizer-astrazeneca-covid-19-vaccines-offer-protection-against

Twist Bio, Regeneron pitch global sequencing test to bring new diversity to large DNA studies

 The synthetic DNA weaver Twist Bioscience has teamed up with Regeneron to deliver a custom next-generation sequencing test that can track minute genetic differences among global populations. 

The goal is to help identify new disease mechanisms and novel drug targets, to boost the drugmaker’s discovery and R&D operations as well as the efforts of international genomics researchers.

In addition, the panel for single-nucleotide polymorphisms—or the individual-letter substitutions known as SNPs—aims to bring new diversity to genome-wide association studies that look to match up underlying variations in DNA with specific diseases and symptoms

According to Twist, the vast majority of studies performed with currently available platforms are based on genetic markers from people of European descent. This incomplete information may be used to underpin a wide variety of genomic tests.

Underrepresentation of global populations in large DNA analyses limits the understanding of how diseases may work and ultimately leads to inequalities in patient care—such as missed diagnoses, or inaccurate risk scores for diseases like cancer among people of different ethnicities.

Using Twist’s next-generation panels, researchers at the Regeneron Genetics Center developed a population genotyping assay that captures globally diverse genetic variations, according to the center’s chief sequencing officer, John Overton.

“This targeted panel integrates into our existing fully automated exome processing workflow and provides base calls and imputed variants whose quality already exceeds the array-based approaches we were using,” Overton said, referring to the test’s accuracy for spotting single-letter changes in the DNA code.

“We began using this panel in late 2020 in the RGC and already we are seeing positive results in our integrated research to better understand the biology of human diseases,” he added.

Now, Twist will begin broadly marketing the formerly internal assay as the Diversity SNP Panel, which includes more than 600,000 DNA probes for capturing about 1.4 million nucleotide variations.

“While SNP microarray has been the gold standard of genetic study, we have more and more customers asking for a complete genotyping solution that allows flexibility for customized disease research and we believe this is the future of disease marker testing,” said Twist CEO Emily Leproust. 

“Collaborating with Regeneron to optimize the assay with content from multiple ethnicities enables increased characterization of diverse populations to improve understanding around disease and potentially therapeutic development as well,” Leproust added.

The assay—marking the first product in Twist’s emerging Targeted Genoytping-By-Sequencing portfolio—also allows researchers to use next-generation sequencers for both genotyping as well as exome and custom panels, rather than having to maintain separate hardware and lab space for the different processes.

https://www.fiercebiotech.com/medtech/twist-bioscience-regeneron-pitch-global-sequencing-test-to-bring-new-diversity-to-large-dna

Novavax CEO: COVID-19 booster to be 'biggest market' in US

 Novavax’s CEO said he believes boosters will be the company’s "biggest market" in the U.S. once it receives regulatory approval for its COVID-19 vaccine. 

"That’ll be probably our biggest market in the U.S. for instance, late this year or next year we expect that it’ll have all the great characteristics of a good boost," said CEO Stanley Erck during an appearance on FOX Business’ "Varney & Company" hours after the biotech company announced that its vaccine was found to be over 90% effective in a clinical trial. 

Erck noted that the timing of the trial saw nearly all infections detected stem from variants, which helped prove effective against strains currently gaining ground in the U.S. and elsewhere including the Alpha and Delta types. 

"The vaccine works, and as they said 93% if you look at just the variants, the vaccine was 93% effective and that’s just terrific I think," he said. 

Following approval, Erck said the company will likely focus on supplying countries outside of the U.S., including fulfilling agreements already made with Canada, Australia, and another to send 1.1 billion doses to COVAX, the COVID-19 Vaccines Global Access program. 

Erck added that the company is already involved in a comparative mix and match trial in the U.K. 

The trial is evaluating safety and effectiveness of vaccine regimens that may include two doses of a mRNA jab and later involve a boost made by a different company. 

"We expect our vaccine to show the most benign side effects and I think we’re going to look good there," he said. "The boosting story is going to be around for many years to come." 

https://www.foxbusiness.com/markets/novavax-ceo-expects-covid-19-booster-biggest-market-us