This work was financially supported
by Alexey Gubarev and the Haxus Foundation

How investments in biotech
can extend your lifespan

Part 1: intercellular matrix

  • Dora Bataeva
  • Nastya Egorova
  • Misha Batin
    Ideologist of the project
  • Irisha Efremova
  • Nodar Lakhuti
    Translated this text from Russian to English
How did we compile this list?
What are these companies? Why these, exactly? Where did we start from?

We started our work with the list of known biomarkers of aging, that, in our view, are important to maintain in a certain range of values - this will help maintain health, improve well-being and achieve maximum life expectancy. We chose our markers as optimal predictors of increasing the likelihood of death.

Today, there are several panels (lists) of biomarkers of aging, ours being one of them - Open Longevity. We constantly monitor and analyse other approaches to diagnostics, but this text was based on ours.

We selected several markers from the panel, which involve the same processes: inflammation, synthesis, and degradation of the extracellular matrix. And then examined the diseases associated with them.

Essentially, these are extreme cases of metabolic pathway breakdowns that accumulate with age (although the diseases discussed in the article are not always age-related). Having compiled a list of the diseases and processes that interest us, we began to look for biotechnological companies that develop relevant therapies.

These companies, unknowingly, or perhaps quite intentionally, are creating what can become part of a global therapy for aging.

For example
Diabetes, a severe case of insulin resistance, as well as fibrosis and some forms of cancer are extreme cases of an imbalance in the synthesis and degradation of the extracellular matrix. We do not claim that the treatment of diabetes, cancer, and fibrosis can help us stay young, but looking in that direction can be helpful, nonetheless.

Another reason to pay attention to these companies is an economic one. Many of the drugs we reviewed have received Fast Track FDA status or Orphan Drug Designation status.

To develop a unique orphan drug and subsequently use it for a wider range of diseases and introduce it to a wider market is a good strategy from an economic point of view.

Orphan diseases are diseases that so few people suffer from that the development of drugs (the so-called orphan drugs) will most likely not pay off and will not bring profit. At the same time, thousands of people suffer from orphan diseases, and they do need help. The state supports the development of orphan drugs by accelerating the process of issuing permits and issuing grants.
Fast Track is designed to facilitate the development of drugs that treat serious or life-threatening conditions and have the potential to address unmet medical needs. The Fast Track status can be requested by the developer from the FDA at any stage of drug development. If the FDA approves the status, then developers can communicate with the FDA more often than when developing a conventional drug, and questions and problems are resolved more quickly. This often leads to the drug being approved by the FDA faster and becoming available to patients sooner.
For example
Rituxan [1, 2] could be one example. The drug was developed jointly by Roche and Biogen and was intended to treat two rare diseases: chronic lymphocytic leukaemia and non-Hodgkin's lymphoma. But later it turned out to be effective for the treatment of rheumatoid arthritis, which is not an orphan disease. Rituxan sales revenue brought Roche nearly $ 8 billion in 2017 and $ 1.4 billion the same year to Biogen. buying shares of such a company you buy a chance to extend your own life.
Obviously, the age-dependent diseases market is especially attractive: we all age, so the products of these companies will always find their consumers.

But there is another reason: by buying shares of such a company you buy a chance to extend your own life.

Aging is an invincible monster. At least, it has always been so, and sometimes this thought paralyzes us. But if you think about it, you and we potentially have many allies—almost all of humanity.

One of the features of age-dependent diseases is their prevalence. For example, in the United States, more than 25% of people over 65 have diabetes [X].

Beyond there being a lot of patients, these diseases are often fatal . In 2016, of the nearly 56.9 million deaths worldwide, 16.2 million were caused by coronary heart diseases and strokes. 3 million people died from chronic obstructive pulmonary disease (COPD) and 1.6 million from diabetes. We have listed only a few age-related diseases, and yet they account for 36.6% of all deaths in the world. And there are also oncological diseases—most of them are also age-related.

If all people joined their efforts and invested in the treatment of diseases that they themselves have, it is possible that medicines could be discovered faster. What will the world look like in which there are no age-dependent diseases? Such a picture may seem a fantasy, but think about universal vaccination, thanks to which people around the world began to live to adulthood instead of dying in childhood.

Financial analysis and aging diagnostics - such a strategy seems optimal to us.
How to choose a company to invest in? From the point of view of potential profitability, we need to predict its capability of bringing the drug to the market. Financial support from other companies is a good sign. Late stage of clinical trials is a good sign, too.

Yet from the point of view of health you also need to assess your risks to develop age-specific diseases. Which diseases are most likely to worsen your quality of life or even become the cause of your death? Is there currently an affordable drug on the market, or is it critically important to develop one and bring it into clinical practice?

Diagnostics of aging is of help here (molecular biological parameters of blood and more that reflect the state of health and risks of age-related diseases at the given moment), family history of diseases, genetic testing... Of course, there is no guarantee of success, but we consider this strategy to be very logical, as it increases the chances of prolonging a healthy period of life and survival in general.

Read more about diagnostic methods here.

So, at last, let's get on with the list of companies which are interesting from the point of view of investments, both for those who just invest in biotechnology, and those who have already been tested for a panel of biomarkers and detected developing health problems.

This article marks the beginning of our analytical work. In the future, we will adjust and improve our strategy. Leave comments, write reviews, and share with us your opinions and information on the state of the market of biotechnological companies. Let's create the list of really promising companies together.

Financial analysis and aging diagnostics - such a strategy seems optimal to us.

This article does not contain any direct recommendations on buying any listed stocks.

Fibrocell Technologies Inc.

Fibrocell Technologies Inc. specialises in cell and gene therapy for skin and connective tissue diseases.

The company's history goes back to 1995. Fibrocell had another name then - Isolagen Technologies - and specialised in development and production of anti-wrinkle medication Laviv. The medication was based on the patient's own cells; fibroblast cells were taken from the patient, cultured ("multiplied") and injected intracutaneously into the nasolabial folds of the patient. Laviv was approved by the FDA in 2011 for cosmetic injections. The drug passed two Phase II clinical trials and five Phase III clinical trials.

Laviv can still be found on the market, but its effect is considered "light, natural" (for example, acne scars are indeed smoothed, but deep and pronounced scars cannot be overcome). The cost is high: $ 2,400 per procedure. A patient needs to wait for about three months until the cells of the drug multiply and reach a sufficient number. Moreover, in order for the effect to be noticeable, several injections are needed - usually three, with a break of six weeks.

Apparently, Laviv did not became popular, and to not to lose the investment it was needed to find another application for the drug, more important than the treatment of nasolabial folds. Fibrocell tried to repurpose Laviv for treatment for scarring of the vocal cords, which leads to chronic or severe dysphonia, but Phase II clinical trials were unsuccessful. In 2016, Fibrocell stopped working on Laviv, cutting 24 jobs. Now the company has 23 employees.

In the same year, Fibrocell and Intrexon Corporation (NASDAQ: XON) began working on a drug for treatment of epidermolysis bullosa: FCX-007. Essentially, FCX-007 is still the same Laviv, that has been subjected to genetic engineering changes. The cell culture technology belongs to Fibrocell, and Intrexon is responsible for the technology for the genetic engineering changes of these cells.

So, Fibrocell put aside the anti-wrinkle medicine and focused all its attention on two orphan drugs and the preclinical development of a medicine for arthritis (chronic joint inflammation). Despite that wrinkles are the most visible external manifestation of aging, older people have more important problems. And these problems involve the extracellular matrix of all organs and tissues, and not just the skin.

Pennsylvania, USA
Year established
Market cap: $18,44 m
Income: -$11,9 m
Revenue: $21,79 m
Matrix metalloproteinases (MMPs)

Number of medications
Two medications overall at the stage of clinical trials:
FCX-007 (Phase III)
FCX-013 (Phase II).

One medication is on preclinical development stage (arthritis)
Diseases the company is focused on
Bullous epidermolysis
(autoimmune skin disease)
What age-related diseases and conditions the medications can be useful for
Fibrosis, first of all, and aging of the body in general, as well as of skin, connective tissues, also, for example, kidneys (organs which functional structures consist of an extracellular matrix).

Why are we interested in these technologies?
Most of the tissues in our body consist not only of cells, but also of the extracellular (intercellular) matrix. And the so-called connective tissues are generally more likely to consist mostly of the matrix, although there are cells too.

The extracellular matrix serves as a mechanical support for the cells and provides their nutrition. It can be imagined as a three-dimensional canvas of structural proteins (mainly collagen, elastin, and a number of others) and filled with liquid. Cells (fibroblasts) are inserted into this canvas, which in turn synthesize extracellular matrix components and various biochemically active molecules.

Collagen production decreases with age: each year there is 1% less collagen produced in the skin of a person older than 20, which explains its thinning. Problems with other components of the matrix also begin to develop.

Matrix metalloproteinases (MMPs) are involved in the disassembly of the extracellular matrix. This is a complex process, but in order to understand its importance, imagine the formation of blood vessels: firstly, a tunnel in the three-dimensional structure of the matrix needs to be made. MMPs play the role of workers punching a hole for such a tunnel. There are 29 different types of metalloproteinases, each has its own number, so in the academic literature they are usually found under names like MMP-1, MMP-8, etc.

Normally, the degradation and synthesis of the matrix are in balance, and the matrix has the optimal properties for each particular tissue: not too hard, not too loose. With age, the balance is disturbed, which is expressed in various diseases, for example, in fibrosis. The latter is a condition in which connective tissue grows forming scars. It has been shown that MMP-1, MMP-8, and MMP-13 can play an antifibrotic role, since an increase in their level decreases liver fibrosis [3, 4, 5].

On the other hand, it has also been shown that excessive production of MMP-1 in smokers causes premature aging of the skin. Therefore, FCX-013 technology, which can be used to regulate the production of metalloproteinases, turn their synthesis on and off, seems to be optimal for combating various fibrosis.

In September 2018, the FDA approved Fast Track status for FCX-013. This therapy is now going through clinical trials Phase I&II (i.e. Phase I combined with Phase II), and volunteers are being called for.


Formerly known as AvidBiologics, Formation Biologics.

A company that develops drugs for cancer and fibrosis, targeted at the molecular pathways TGF-β and EGFR (the main culprits of oncological diseases and fibrosis: the fact which there is enough evidence for).

TGF-β is a transforming growth factor beta, a multifunctional signalling molecule secreted by white blood cells. One of its key functions is the regulation of inflammatory processes. TGF-β also plays an important role in stem cell differentiation. There is also a number of other functions, as is often the case in biology.
EGFR is a transmembrane receptor that can respond to epidermal growth factor (EGF), binding it. EGF is a protein that stimulates the growth of cells in many tissues as well as cell differentiation.
Austin (Texas, USA) and Montreal (Canada)
Year established
TGF-β (трансформирующий фактор роста бета)
Number of medications
We took interest in just one, but in total the company has four drugs at the stage of clinical trials.

Diseases the company is focused on
Solid cancers, fibrosis
What age-related diseases and conditions the medications can be useful for
Cancer, osteoarthritis, myocardial infarction, fibrosis
Why are we interested in this technology? TGF-β and myocardial infarction
There are several diseases, beside cancer, the development of which TGF-β plays an important role in. For example, its level rises with myocardial infarction, which exacerbates the development of the disease.

Myocardial infarction - damage to the heart muscle due to blockage of one of the arteries of the heart. Insufficient blood supply leads to the immediate death of cardiomyocytes, and then fibrosis and formation of scar tissue, which further leads to myocardial dysfunction and heart failure.

Concerning heart fibrosis, TGF-β is a "Jack of all trades": it can trigger apoptosis in cardiomyocytes and control the conversion of heart fibroblasts to myofibroblasts, which produce extracellular matrix components and repair damaged tissue. But if the process gets out of control, myofibroblasts begin to secrete too many components of the matrix, which replaces muscle tissue. As a result, fibrosis develops; part of the heart tissue is replaced by a connective one that has no function there.

Sanofi Genzyme

The double name, Sanofi Genzyme, is not accidental. In February 2011, the French pharmaceutical giant Sanofi-Aventis bought Genzyme (along with the technology we are interested in) for $ 20.1 billion. A little later, in May 2011, the giant simplified its name to just Sanofi. And now there is a subsidiary Sanofi Genzyme in the Sanofi family.

Jumping ahead, we would like to add that Sanofi took part in the fate of another company in our list. Sanofi had bought not that company itself, though, but a whole set of drugs from it: Sanofi agreed to incur development costs, as the inventor company could not independently complete the first phase of clinical trials, and to share the profits. We are going to tell the whole story later.

Genzyme, at the time it was bought by Sanofi-Aventis, was the third largest biotechnology company in the world: it employed more than 11,000 people, and its net profit in 2010 was $ 400 million (with the revenue of $ 4 billion). By this time, enzyme therapy had brought the company about 40% of its revenue - the portfolio managed by the Personalized Genetic Health division was the largest of the five operating units. The company sold the Genzyme Genetics division for $ 925 million to LabCorp the same year. The director of LabCorp said then that it was one of the leading genetics and oncology laboratories in the United States.
The part of the history of Genzyme we are interested in begins with the medication called Fresolimumab (aka GC1008): a monoclonal antibody that binds and inhibits all TGF-β isoforms. This human antibody and immunomodulator is intended for the treatment of (1) idiopathic pulmonary fibrosis, (2) focal segmental glomerulosclerosis, (3) kidney cancer, and (4) skin (melanoma).

The drug was discovered by scientists from the Cambridge Antibody Technology (CAT) laboratory and was one of two candidates for the treatment of scleroderma (the one we wrote about above). The CAT team selected metelimumab (CAT-192) and fresolimumab to be developed together with Genzyme. In 2005, after unsuccessful clinical trials, CAT and Genzyme decided to abandon metelimumab in favour of fresolimumab.

In February 2011, Genzyme became a part of Sanofi Genzyme (although the process of transfer of powers began in November 2010, as shown in the figure on the right), and in June the same year fresolimumab was tested on patients suffering from idiopathic pulmonary fibrosis, focal segmental glomerulosclerosis, or cancer. A list of all clinical trials of the drug, registered in the USA, can be found here.

Sanofi Genzyme now has an impressive list of drugs (about 50) at the clinical trials stage. Most of them are monoclonal antibodies.

The history of Genzyme:
What company bought what company and when (click on the image to enlarge)
Sanofi (France)
Year of the merger with Sanofi
12,000 at the time of the merger with Sanofi
Sales for the fourth quarter of 2018
7,228 m
TGF-β (transforming growth factor beta)
Number of medications
More than 50 in development and clinical trials stages and 25 have already been approved by the FDA
Diseases the company is focused on
Idiopathic pulmonary fibrosis, focal segmental glomerulosclerosis, kidney cancer, and melanoma
Для каких возрастных заболеваний и состояний может пригодиться
Рак, фиброз, остеоартрит
What technology interests us and why?
To tell the truth, at first, we were interested in fresolimumab. But its capacity to inhibit all isoforms of TGF-β can interfere with therapy (as is described above), so, to inhibit TGF-β, we are considering the product that is being tested by the Forbius, the company that precedes Sanofi Genzyme in our list.

However, having carefully looked at Sanofi Genzyme's portfolio, we found another interesting drug - SAR339375 (RG-012), intended for the treatment of Alport syndrome, which is an siRNA-21 oligonucleotide (antimiRNA-21). In the future this technology will probably also help in the treatment of fibrosis and cancer. And that is the second known case when Sanofi took part in the fate of another company in our list and in the development of a medication that is of interest to us.

Sanofi Genzyme is a huge corporation. Let's take a closer a look at this second case, of the company Regulus Therapeutics, which originally developed RG-012, in another text below.

Regulus Therapeutics

Биофармацевтическая компания, занимается разработкой олигонуклеотидов, направленных на связывание микроРНК.
MicroRNAs are small RNA molecules, usually 20–25 nucleotides in length, that do not encode proteins but regulate gene expression (that is, the process of protein production).

In academic literature, the names of these molecules look like the prefix miR followed by a hyphen followed by a number, e.g. 'miR-21'. A number simply indicates when a given molecule was discovered, that is, miR-752 was discovered later than miR-751 and earlier than miR-753. 1800 microRNAs had been discovered overall by 2014.
The goal of microRNA-based therapy is to suppress specific microRNAs (or miRNAs). Experiments on animal models have shown that this therapy works for cardiovascular disease, cancer, and hepatitis C.
An oligonucleotide is a short fragment of RNA or DNA obtained either by synthesis or by cleavage of a fragment from a large chain (oligo is the Greek for "a little"). In miRNA-based therapy, such short fragments are needed that would specifically (complementarily) bind to miRNA, thereby blocking its activity.

Carlsbad, California, USA.

Parent organizations: Alnylam Pharmaceuticals, Ionis Pharmaceuticals
Year established
Number of employees
Market cap: $12,653млн
Income: -$27 m
Revenue ttm: $6,8 m
Number of medications
Two medications overall, we are interested in one of them, RG-012
Disease the company is focused on
Alport syndrome
What age-related diseases and conditions the medication might be useful for
Fibrosis, cancer
Why this technology interests us?
More and more data indicate that miR-21 can play an important role in the development of fibrosis, contributing to the division of fibroblasts and increasing the production of extracellular matrix components [8, 9]. In fibrotic diseases, expression of miR-21 is elevated and it can be used as a potential diagnostic and prognostic marker, and even as a therapeutic target.


The company specializes in cell and gene therapy for skin and connective tissue diseases.

The company has developed a unique technology based on patients' own fibroblasts: cells are taken from the patient's skin, subjected to genetic engineering changes, and administered back to the same patient. This way gene therapy becomes 'localised', which increases efficiency and reduces side effects.

The new drug should prove effective and safe in the course of the Phase III of clinical trials, which is conducted with a large group of people. Also, in order to be approved by the FDA, the new drug must be better (more effective, safer, more convenient) of all existing drugs intended for the treatment of the same diseases. For roxadustat, epogen was such a competitor.
It was officially stated that there is no clinically significant risk difference between the drugs: "We believe there is no clinically meaningful difference in risk". This discrepancy made investors doubt the safety of the drug. Most likely, the risks are about the same. For some groups of patients roxadustat was slightly more effective than epogen, so analysts predict that the FDA is likely to approve roxadustat. Still, the investors are disappointed: since Roxadustat turned out to be only marginally better than epogen, a drug with thirty years of experience, sales of a new drug might be slow and would not bring a lot of money.
In 2017, another drug, pamrevlumab, caused quite a stir, successfully passing the second phase of clinical trials. Fibrogen shares then rose 1.5 times.

Generally, the mere fact that a company's shares are rising or falling does not mean anything. It rather reflects the degree to which society hopes for the success of the drug. Pamrevlumab is indeed a promising drug, and we are going to tell more about it.
San Francisco (California, USA)

Additional offices: Beijing and Shanghai (China)
Year established
Number of employees
Market cap: $3,984 b
Income: $49.00 m
Revenue ttm: $352,50 m
CTGF (connective tissue growth factor)
Number of medications
We are interested in Pamrevlumab, one of the three company's medications
Disease the company is focused on
Idiopathic pulmonary fibrosis (IPF), pancreatic cancer, Duchenne muscular dystrophy
What age-related diseases and conditions the medication can be useful for
IPF itself is an age-related disease. It is also possible that the drug will be helpful in Alzheimer's disease.
The drug, thanks to which the company's shares jumped in 2017, is pamrevlumab. It is intended for the treatment of idiopathic pulmonary fibrosis (IPF), that is, pulmonary fibrosis of unknown origin.

IPF is a chronic, progressive lung disease in which normal tissues are gradually replaced by scar tissue and so the lungs gradually lose their ability to effectively transfer oxygen to blood.

The disease usually affects older people of ages between 50 and 70. The prevalence rate is 12 to 20 cases per 100,000 people, and about 40,000 cases are recorded annually in the United States alone. Life expectancy of most patients after the diagnosis of IPF is 3-5 years but can vary between several months and tens of years.

Risk factors for developing IPF include old age (most patients are older than 50), smoking, acid reflux (about 75% of patients with IPF suffer from it), and a genetic predisposition.

IPF begins with a continuous inflammation in the lungs. For example, in the case of acid reflux, the patient constantly inhales tiny droplets of acid that damage the alveolar epithelial cells. Constant inflammation develops, cytokines and growth factors are activated, which leads to fibrosis (see the figure in the part "Why").

Foresee Pharmaceuticals Co., Ltd.

FP has two core technologies: Drug Delivery Technology and Rational Drug Design. The company's main drugs are FP-001, which is used to treat prostate cancer, and FP-025, which is designed to treat asthma and COPD.
Asthma is a chronic inflammatory disease of the respiratory tract. External irritants cause airways contraction, swelling, and mucus secretion. As a result, the airways narrow making breathing difficult.
Chronic obstructive pulmonary disease (COPD) is a lung lesion that develops as a response to prolonged exposure to irritating agents (tobacco smoke, air pollution) and the associated chronic inflammation.
Taipei City, Taiwan и Newark, Delaware, USA
Year established
Number of employees
Market cap
$228 m
Matrix metalloproteinase (MMP)
Number of medications
Seven drugs overall at various stages from development to research, we are interested in just one
Disease the company is focused on
Asthma and chronic obstructive pulmonary disease (COPD)
What age-related diseases and conditions the medications can be useful for
COPD and arterial stiffening
What technology interests us?

We liked the FP-025 medication, an inhibitor of metalloproteinase 12 (MMP-12).

The drug has successfully passed the first phase of clinical trials (NCT03304964) and is now in the second phase (NCT03858686).

FP-025 suppresses the operation of MMP-12. The latter is a key enzyme that directs inflammatory cells and plays an important role in the development of asthma and COPD.

MMP-12 is an enzyme that promotes the cleavage of peptide bonds within the peptide chain. It is effective primarily against elastin (an extracellular matrix elastic protein), for which reason it is also called elastase. But it also breaks down other extracellular matrix proteins, including type IV collagen, fibronectin, laminin, and others.

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