Nobel Prize History
The Nobel Prize is the most prestigious award in the scientific world. It was created according to Mr. Alfred Nobel’s will to give a prize “to those who, during the preceding year, have conferred the greatest benefit to humankind” in physics, chemistry, physiology or medicine, literature, and peace. A sixth prize would be later on created for economic sciences by the Swedish central bank.
The decision of who to attribute the prize to belongs to multiple Swedish academic institutions.
Legacy Concerns
The decision to create the Nobel Prize came to Alfred Nobel after he read his own obituary, following a mistake by a French newspaper that misunderstood the news of his brother’s death. Titled “The Merchant of Death Is Dead”, the French article hammered Nobel for his invention of smokeless explosives, of which dynamite was the most famous one.
His inventions were very influential in shaping modern warfare, and Nobel purchased a massive iron and steel mill to turn it into a major armaments manufacturer. As he was first a chemist, engineer, and inventor, Nobel realized that he did not want his legacy to be one of a man remembered to have made a fortune over war and the death of others.
Nobel Prize
These days, Nobel’s Fortune is stored in a fund invested to generate income to finance the Nobel Foundation and the gold-plated green gold medal, diploma, and monetary award of 11 million SEK (around $1M) attributed to the winners.
Source: Britannica
Often, the Nobel Prize money is divided between several winners, especially in scientific fields where it is common for 2 or 3 leading figures to contribute together or in parallel to a groundbreaking discovery.
Over the years, the Nobel Prize has become THE scientific prize, trying to strike a balance between theoretical and very practical discoveries. It has rewarded achievements that built the foundations of the modern world, like radioactivity, antibiotics, X-rays, or PCR, as well as fundamental science like the power source of the sun, the electron charge, atomic structure, or superfluidity.
Collateral damages
A major issue in cancer treatment is that cancer is unlike any other disease involving an out-of-control growth of dangerous cells.
Viruses, bacteria, and parasites are all foreign organisms attacking the human body, so the pathogens all have significant differences in their cellular structure. This means that drugs and treatments that work against infectious diseases can damage them without interacting with the human cells.
In contrast, cancer is made of body cells that have lost their normal programming and are multiplying out of control. But any drugs that affect or kill cancer cells will also, to some extent, affect the rest of the body.
This is a problem with treatments like chemotherapy (Nobel Prize in Medicine in 1988), which, while affecting more cancer cells, also come with plenty of side effects. Some other cancer therapies can work, especially against specific situations of cancer. For example, surgery for very compact cancers, replacing all the bone marrow stem cells in leukemia (Nobel Prize in Medicine in 1990), or hormone treatment for prostate cancer (Nobel Prize in Medicine in 1966).
However, other types of cancer, or cancer that has reached the stage of metastasis, will usually not be curable with these treatments. So, a much more subtle treatment than drug molecules that destroy cell walls or block protein production is needed. Ideally, one with a targeting system is able to distinguish between a normal cell and a cancer cell.
James P. Allison and Tasuku Honjo finally made such a discovery, which was awarded the Nobel Prize in Medicine in 2018.
Source: Nobel Prize
Leveraging The Immune System
Luckily, the human body already has such a system available in the form of immune cells. The immune system’s fundamental mechanism is to differentiate between self (the human cells) and non-self (bacteria, viruses, fungi, etc). It is tightly regulated by chemical signals (often proteins) activating or inhibiting the immune response, helping to boost response against infections while also avoiding auto-immune reactions damaging healthy tissues.
We also know that the immune system is somewhat able to detect cancer cells as abnormal, spotting the changes that turn a healthy cell into cancer and “labeling” it as non-self. In the 1990s, some molecules downregulating immune cells (T-lymphocytes) were discovered and investigated for their potential in solving auto-immune diseases. However, other researchers realized that they could be utilized in cancer patients instead.
CTLA-4
James P. Allison was studying the T-cell protein CTLA-4, a T-lymphocyte protein that reduces the immune system’s activity. He had developed an antibody that neutralized CTLA-4. So he started investigating if neutralizing CTLA-4 could lead to increased immune activity, and target cancer in the process.
In 1994, his team discovered that neutralization of CTLA-4 could cure cancer in lab mice.
Source: Nobel Prize
From then on, efforts would go on to develop the lab results into an actual human therapy. This would take a while, with questions about the dosage, safety profile, and best cancer to target to be solved.
Nevertheless, sciences around CTLA-4 made continuous progress, and in 2010, a large clinical study showed strong results for patients suffering from melanoma, an aggressive form of skin cancer. It would lead to approval of the therapy by the FDA in 2011, with Ipilimumab commercialized by Bristol-Myers Squibb (BMY – see below for more detail about the company).
This discovery would form the base template for an entirely new type of cancer therapy: “checkpoint-blocking antibodies.”
PD-1
A few years before James P. Allison, Tasuku Honjo discovered a protein he called PD-1 on the surface of T-cells. Over years of research, he discovered the now well-understood fact that PD-1 expression is a hallmark of “exhausted” T cells. This state of exhaustion, which occurs during chronic infections and cancer, is characterized by T-cell dysfunction, resulting in suboptimal control of infections and tumors.
Therefore, blocking PD-1 from functioning can reactivate the immune system and make it attack the cancer cells. It is worth noticing that while conceptually similar, PD-1 mechanisms are entirely different from CTLA-4.
Source: Cancer Cell Interantional
Similar to CTLA-4, years of research and clinical trials would finally yield FDA-approved therapies following a key clinical study in 2012.
This includes Nivolumab, approved for patients with metastatic, refractory non-small cell lung cancer and commercialized by Bristol-Myers Squibb under the name Opdivo, and Pembrolizumab for patients with advanced or metastatic melanoma, commercialized by Merck under the name Keytruda.
Limits Of Checkpoint-Blocking Antibodies
These cancer therapies have since approval saved many lives, but they are not (yet?) perfect. This is why they are often used in cases of aggressive, metastatic cancers, where the outcome was almost certain death until a few years ago.
One limitation is that the treatment works by essentially overstimulating the immune system. While this is very useful in the case of aggressive and metastatic cancer, this is also the very thing CTLA-4 and PD-1 are trying to avoid in a healthy human body. This is because a too-active immune system can start attacking not only infection and cancer cells but also healthy tissues.
This can cause side effects like skin rashes or bowel irritations, to rare but serious issues like internal organs inflammation or damage to endocrine glands that can have permanent consequences.
Future Of Checkpoint-Blocking Antibodies Therapies
PD-1 and CTLA-4 were only the first therapies in their class, with many more similar concepts and immunological mechanisms of T-cell inhibition found since, and undergoing clinical trials.
In parallel, combination therapies mixing together PD-1 & CTLA-4 are being investigated for cancer forms that resist the treatments when used separately. This could be especially useful for solid tumors, where the immune system struggles to act.
There is also hope that improving results can be achieved by combining these therapies with other treatments, such as other cancer drugs or radiation therapy.
Other strategies to improve treatments based on checkpoint-blocking antibodies could be to have them act only in targeted parts of the body or activate them only in the presence of cancer cells.
Investing Into Checkpoint-Blocking Antibodies Therapies
The discovery of CTLA-4 and PD-1 opens the way to novel ways of treating cancer by leveraging the immune system. Because these therapies are remarkably efficient in cases that were essentially a death sentence before, they are also very profitable business lines, not directly competing with most pre-existing cancer therapies.
As more clinical trials are done and better optimization of the therapeutic protocols is achieved, new types of cancers and reduced toxicity can be achieved, leading to a growing market for these treatments.
You can invest in cancer-related companies through many brokers, and you can find on this website our recommendations for the best brokers in the USA, Canada, Australia, the UK, as well as many other countries.
Besides the companies discussed below, you can also find potential investing ideas in our article “Top 10 Cancer Therapy Stocks”.
If you are not interested in picking specific pharmaceutical companies, you can also look into cancer ETFs, especially those focused on immunotherapies like the iShares Genomics Immunology and Healthcare ETF (IDNA) or the Loncar Cancer Immunotherapy ETF (CNCR) to capitalize on the growth of the immunotherapy market as a whole, and the immunomodulators discussed in this article in particular.
Source: Grand View Research
Immunotherapy Companies
1.Bristol-Myers Squibb Company
BMS is a company with a long-established presence in oncology, which was reinforced by the acquisition of Celgene in 2019.
In October 2023, it also acquired Mirati Therapeutics for $5.8B (an all-cash transaction, through cash and debt), accessing the company’s portfolio of lung, liver, and pancreatic cancer therapy. The deal should be closed by H1 2024.
BMS’s R&D effort combined with this acquisition has strongly boosted the company’s portfolio, with its new products growing rapidly, more than tripling since 2021. The “in-line brands” have also grown by 7% year-to-year.
Source: BMS
The company’s R&D pipeline is dominated by oncology, as 50 out of 71 therapies in development are targeting cancer, with a focus on solid tumors, lymphoma, and myeloma.
Overall, we could say that the company’s focus on immunology and oncology has paid off, with good results from the R&D efforts. It also feeds the company’s pipeline by providing it with a deep understanding of the cause of cancer and possible targets it can aim towards for new therapies.
It is also expanding the possible application of its existing drugs, for example, Opdivo, the initial CTLA-4 drug, was newly approved in 2024 for “First-Line Treatment of Adult Patients with Unresectable or Metastatic Urothelial Carcinoma”.
This oncology focus also pays off in terms of manufacturing, with new therapies requiring advanced facilities to produce custom cell lines and/or monoclonal antibodies.
BMS has been rising quickly since 2018 and has become one of the leading companies in oncology. This position will likely persist for the next few years and be highly profitable for its shareholders.
2. Merck
Merck is a company with a history of innovation and capitalizing on what would later yield Nobel Prize, as we saw regarding the anti-parasite medicine ivermectin in our article “Investing in Nobel Prize Achievements – Drugs to Battle Crippling Parasites.”
Merck was also the leading force in commercializing the PD-1 inhibitor drug Pembrolizumab for patients with advanced or metastatic melanoma, commercialized by Merck under the name Keytruda.
The drug has become a best seller in oncology, making 43% of Merck’s total revenues in early 2024. The rest of the company’s revenues mostly come from vaccines (Merck is the #1 spot for non-COVID-19 vaccine sellers) and infectious diseases segments.
Source: Merck
Keytruda’s explosive growth was driven by Merck pursuing a strategy of aggressively expanding Keytruda’s approved applications since 2021, which is starting to bear fruit.
The drug is now approved for cancer in the lungs, kidneys, skin, breast, cervix, and bladder.
Source: Merck
This has moved the company’s portfolio from a late-stage cancer focus to a more broad approach across the disease’s stages. This only demonstrated a unique feature of Keytruda, as the only immuno-oncology drug with increased survival in four earlier-stage cancers.
The evolution of Merck into a leader in oncology is ongoing, with 2.6 million patients treated so far and 30,000+ patients in 30 different phase III clinical trials (the last phase before potential approval by the FDA).
Merck has been a remarkably innovative company for a pharmaceutical giant, with no less than 2 Nobel Prize-winning products in its portfolio: Keytruda in oncology, and ivermectin in anti-parasite therapies.
It is now re-investing these revenues to develop an extensive oncology product line while expanding its vaccines and infectious diseases leadership. Both are therapeutic fields that require better treatments and affect large sways of the population, likely leading to future growth for the company.