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Equity Perspectives

In the fast-moving field of genetics and genomics, innovation has expanded the potential for substantially more effective medicines against a wider variety of diseases.  

 

 

In Brief:

  • Thanks to the plummeting cost of sequencing the human genome, significant progress in identifying genetic defects has led to breakthrough diagnostics and preventive medicines, as well as targeted drug therapeutics, some of which deliver corrective genes into a patient's own diseased cells.
  • The pace of this advance is breathtaking, compared to Moore’s Law, which enabled the computer revolution; genetic sequencing now has sharply outpaced this.
  • Both the federal Food and Drug Administration and Medicare have clarified the regulatory pathway for genetic health tests to hit the market.
  • Assessing the surging momentum of three interrelated technologies (gene therapy, genetically engineered cell therapy, and gene editing), Goldman Sachs analysts project an eventual “one-time” total addressable market of $5 trillion for genome medicine, with the potential to expand further.
  • While a greater understanding of cancer triggered by mutations has grabbed the most attention, some companies’ genetic and genomics research has led to potential treatments of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and ALS (amyotrophic lateral sclerosis).
  • With the confluence of Big Data, high-performance computing, and very clever algorithms, artificial intelligence techniques should continue to drive personalized medicine by much faster decoding of the genomes of various diseases. The potential to modulate such organisms is phenomenal.

 

While large-cap technology stocks were selling off recently, Lord Abbett investment professionals remained focused on modern medicine plays with significant growth potential. Among the most notable examples was a ground-breaking manufacturer of genomic analysis products as well as smaller-cap biopharma companies in the burgeoning field of targeted therapies.  

For simplicity’s sake, let’s call the first company “Sequencer.” In the last five years, Sequencer’s stock price has quadrupled (as of April  6, 2018), thanks to sequencing equipment that enables a wide variety of applications, allowing researchers to ask virtually any question related to the genome (complete set of genes), transcriptome (sum total of messenger RNA molecules), or epigenome (a multitude of chemical compounds that can tell the genome what to do) of any organism.

Now that the cost of sequencing a single human genome has dropped, from $100 million in 2001 to around $1,000 in 2017 (see Chart 1), some analysts expect the global DNA-sequencing market to experience substantial double-digit growth during the period 2018–22. As a result, the potential for treating not only genetic diseases but also other diseases, with more personalized strategies by editing DNA, is greater than ever.

Since powerful sequencing technologies helped unlock the power of the genome (see Chart 2), the leading sequencing-equipment company now serves research and clinical customers in a broad range of markets, including oncology, forensics, genetic diseases, reproductive health, agriculture, and microbiology.  It has enabled the adoption of genomic solutions at universities and academic research centers; genome centers; hospitals; government agencies; and pharmaceutical, biotechnology, and consumer genetics companies.

Perhaps you’ve seen print and television ads promising to unlock your genetic heritage for a few hundred dollars. That’s just a preview of increasingly sophisticated services to come. As one sequencing company executive put it, “Discoveries that were unimaginable a few years ago are now becoming routine.”

 

Chart 1. The Cost of Sequencing a Human Genome Has Plummeted Since 2001


Source: National Human Genome Research Institute.
Note: To illustrate the significant decline in DNA sequencing costs, this chart shows hypothetical data reflecting Moore’s Law, which, in its simplest form, states that processor speeds, or overall processing power for computers, will double every two years. It is widely believed that technology improvements that keep pace with Moore’s Law are doing exceedingly well, making it useful for comparison, according to the National Human Genome Research Institute.

 

Chart 2. Key Events in the Evolution of Genomic Medicine

Source: Goldman Sachs Global Investment Research.

 

New Weapons in the War on Cancer

“Cancer is a disease of the genome. Every person’s cancer is different and every tumor has its own unique abnormalities at the genetic level. Some of these abnormalities are clinically significant and, if identified, can be exploited to improve cancer detection, management and treatment.”

—Andrew Futreal, Ph.D., Chair, Genomic Medicine, M.D. Anderson Cancer Center

Each human body contains more than 37 trillion cells of all shapes and sizes. Each cell normally contains 23 pairs of chromosomes and three billion base pairs of DNA, which is made up of four smaller molecules called nucleotides. Each strand of DNA is six feet long, packed into a nucleus that is 10 micrometers in diameter. Cancer begins when a normal cell mutates, or changes, and is not able to repair itself. Treating that cancer without damaging healthy cells has been the challenge for ages.

Targeted therapies have become a cornerstone of precision medicine in the “war” on cancer. These therapies use information about a person’s genes and proteins to prevent, diagnose, and treat disease. But much depends on the identification of good targets—that is, targets that play a key role in cancer cell growth and survival.

Among the stocks that have advanced the most this year on their strength of the targeted therapies are:

  • A clinical-stage gene therapy company that focuses on commercializing novel treatments for patients suffering from rare and life-threatening neurological genetic diseases.  A pharmaceutical giant recently announced plans to acquire the company at an 88% premium, with an eye toward global distribution as soon (and as safely) as possible.
  • A company that is applying its expertise in cellular metabolism, biology, and genomics to transform the lives of patients with cancer and rare genetic diseases.  In the 12 months ended April 9, 2018, its stock jumped 49.1%, outperforming the industry’s increase of 11.4%.    
  • A young company that is developing a new generation of highly selective and potent kinase (protein) inhibitors, based on a deep understanding of the genetic blueprint of cancer. The company believes its ability to identify the drivers of disease, coupled with its proprietary library of novel and diverse chemical compounds, helps it develop kinase therapies against new and difficult-to-drug targets.
  • A firm that specializes in highly selective medicines for patients with genetically defined cancers. Based on clinical studies, some investors are betting that kinase inhibitors developed in this fashion might eventually be able to combat two or more cancers that are uniquely dependent on single-gene abnormalities in the same patient.
  • A “molecular insights” company with a massive genomic-profiling platform that helps it understand the minutest intricacies of a patient's tumor. Its tests provide biomarker information, which in turn can steer doctors and patients toward approved targeted therapies, immunotherapies, and clinical trials. This approach is just starting to gain momentum.

Brain Matters
One of the more interesting genomics plays of late has been a biopharmaceutical company we’ll call “3B,” which is developing a broad portfolio of therapeutic candidates for neurodegenerative diseases, including Alzheimer’s, an incurable illness that causes progressive decline in memory and other aspects of cognition. Alzheimer’s is currently the sixth-leading cause of death in the United States, and as the baby-boom generation grows older, the financial impact on Medicare and Medicaid could be severe.

3B recently announced that it had begun dosing of its small molecule inhibitor in a Phase 1 clinical trial in healthy volunteers, and achieved proof of concept of its large molecule blood-brain barrier-delivery platform technology in nonhuman primates. It also is collaborating with a large Japanese pharmaceutical company to expand its blood-brain barrier-delivery technology platform with a new generation of antibody therapeutics.

Looking Ahead
We believe investors have not fully appreciated the potential to translate science into life-changing genome medicines. Of course, there are risks—a disappointing clinical trial can cause a biotech stock to plummet—but as genome medicine becomes more precise and effective, the growth prospects should be significant, given the staggering costs of the world’s most serious diseases.  Some small companies in this space could grow into much larger entities, or become acquisition targets for major biopharmaceutical makers.

The costs of research and development in this sector are formidable and likely to keep increasing. As new genome therapies are developed and placed in clinical trials, regulators may ask myriad questions, such as: What is the right number of patients for such trials?  Which hurdles are most important?  If the companies clear the most important hurdles, there is still the risk that some payers may not understand the value of cutting-edge therapies, in which case companies must decide whether they should spend vast amounts of capital to moving their science forward.  If there’s a gap, patients may die.1

Most chronic disorders require lifelong treatment, but Goldman Sachs analysts believe gene and cell therapies have the potential to be "one-shot cures," or at the very least, less-frequent treatments, targeting diseases at the genetic level. (See Table 1.)

“While they are being tested (and proven effective) as treatments of ‘last resort,’ these therapies could next move into earlier stages of disease progression, which would disrupt existing therapeutic markets,” the Goldman team said. “In diseases where there are no current treatment options (many rare diseases), new profit pools are formed.”2

Whatever timetable such profitability takes, assessing the long-term prospects, challenges, and risks facing innovative companies in the genomic revolution will require close collaboration among active managers and astute research analysts. The players may change; the leaders may change; but now, the tools for drug discovery are more precise than ever. All of which suggests a growth river that should flow for years.

—Reported by Steve Govoni

 

Table 1. Genome Medicine: Three Interrelated Technologies

Source: Goldman Sachs Global Investment Research.

 

1 Nick Leschly, “Gene Therapy: The Time Is Now,” TEDxBoston, June 22, 2012.
2 Salveen Richter, Richard Yeh, Ross Weinraub, Kevin Patel, Alexana Astor, “Profiles in Innovation: The Genomic Revolution,” Goldman Sachs Global Investment Research, April 10, 2018.

Glossary
A genome comprises the complete DNA (deoxyribonucleic acid) in an organism, including its genes. Genes carry information for making all the proteins required by all organisms. These proteins determine, among other things, how the organism looks, how well its body metabolizes food or fights infection, and sometimes even how it behaves. (Source: Oak Ridge National Laboratory.)

The transcriptome is a collection of all the genetic instructions present in a cell. Such “transcripts” may serve to influence cell structure and to regulate genes.

The epigenome is a multitude of chemical compounds that can tell the genome what to do. (Source: National Human Genome Research Institute [NHGRI].)

Personalized medicine refers to the tailoring of medical treatment to the individual characteristics of each patient. It also refers to the classifying of individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not.

RNA, or ribonucleic acid, is a molecule similar to DNA (deoxyribonucleic acid). Unlike DNA, RNA is single-stranded. An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases: adenine (A), uracil (U), cytosine (C), or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). More recently, some small RNAs have been found to be involved in regulating gene expression. (Source: National Human Genome Research Institute.)

DNA, or deoxyribonucleic acid, is the chemical name for the molecule that carries genetic instructions in all living things. The DNA molecule consists of two strands that wind around one another to form a shape known as a double helix. Each strand has a backbone made of alternating sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of four bases: adenine (A), cytosine (C), guanine (G), and thymine (T). The two strands are held together by bonds between the bases; adenine bonds with thymine, and cytosine bonds with guanine. The sequence of the bases along the backbones serves as instructions for assembling protein and RNA molecules. (Source: National Human Genome Research Institute.)

DNA sequencing is the process of determining the precise order of the four nucleotides, namely, adenine, guanine, cytosine, and thymine, in a strand of DNA.

Resources

Precision Medicine in Cancer Treatment

Tumor DNA Sequencing in Cancer Treatment

Targeted Therapy to Treat Cancer

IMPORTANT INFORMATION
Keep in mind that all investments carry a certain amount of risk including possible loss of the principal amount invested.  The value of investments in equity securities will fluctuate in response to general economic conditions and to changes in the prospects of particular companies and/or sectors in the economy. Historically speaking, growth and value investments tend to react differently during the economic cycle. Since value stocks are often cyclical in nature, they may benefit from the increased spending that usually occurs during an economic expansion. Growth stocks may also perform well during an expansion, but they may also be out of favor during market downturns, when investors pay more attention to price ratios. While growth stocks are subject to the daily ups and downs of the stock market, their long-term potential as well as their volatility can be substantial.

The data contained herein is being provided for informational purposes only and is intended to illustrate certain information analyzed during the research process. It does not constitute a recommendation nor investment advice, and should not be used as the basis for any investment decision.  This is not a representation of any securities Lord Abbett purchased or would have purchased or that an investment in any securities of such issuers would be profitable.

This commentary may contain assumptions that are “forward-looking statements,” which are based on certain assumptions of future events. Actual events are difficult to predict and may differ from those assumed. There can be no assurance that forward-looking statements will materialize or that actual returns or results will not be materially different from those described here.

Statements concerning financial market trends are based on current market conditions, which will fluctuate. There is no guarantee that markets will perform in a similar manner under similar conditions in the future.

The information provided is not directed at any investor or category of investors and is provided solely as general information about Lord Abbett’s products and services and to otherwise provide general investment education. None of the information provided should be regarded as a suggestion to engage in or refrain from any investment-related course of action as neither Lord Abbett nor its affiliates are undertaking to provide impartial investment advice, act as an impartial adviser, or give advice in a fiduciary capacity. If you are an individual retirement investor, contact your financial advisor or other fiduciary about whether any given investment idea, strategy, product or service may be appropriate for your circumstances.

The opinions in this article are as of the date of publication, are subject to change based on subsequent developments, and may not reflect the views of the firm as a whole. The material is not intended to be relied upon as a forecast, research, or investment advice, is not a recommendation or offer to buy or sell any securities or to adopt any investment strategy, and is not intended to predict or depict the performance of any investment. Readers should not assume that investments in companies, securities, sectors, and/or markets described were or will be profitable. Investing involves risk, including possible loss of principal. This document is prepared based on the information Lord Abbett deems reliable; however, Lord Abbett does not warrant the accuracy and completeness of the information. Investors should consult with a financial advisor prior to making an investment decision.

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The Lord Abbett Growth Leaders Fund Class A seeks to deliver long-term growth of capital by investing primarily in stocks of U.S. companies. Learn more.

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