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Cancer vaccines; promise becomes reality?
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The premise of harnessing the power of a patient’s immune system to kill cancer cells is more than 100 years old. In 1891, Dr. William Coley, a surgeon affiliated with the Memorial Sloan Kettering in New York City, developed an immunotherapy for the treatment of cancer based on bacterial toxins. This was the first attempt to use a cancer vaccine. Today, Dr. Coley is known as the “Father of Cancer Immunotherapy”.
The Birth of Cancer Vaccines – An Old Story Becomes New Again. After failing to save the life of an 18 years old woman with sarcoma, a type of cancer, in the year 1891, Dr. Coley was affected deeply and dedicated himself to find a cure for the disease. He found that sarcoma patients concomitantly suffering from a skin bacterial infection known as erysipelas (caused by group A streptococcus bacteria), have undergone spontaneous regression of their cancers. Dr. Coley thought that causing a bacterial infection could help combat cancer in these patients. He injected the erysipelas germ into the tumor of a 35 years old man suffering from head and neck cancer. The treatment worked. The first cancer vaccine was born.
In Recent Years, Results in Human Clinical Trials with Cancer Vaccines Have Been Disappointing. Despite of the robust rationale behind the use of cancer vaccines for the treatment of cancer, the long history behind this medical hypothesis, the search for the “Holy Grail” (a curative cancer vaccine) has been elusive. Over the last twenty years, cancer vaccines have been a disappointing segment of the biotechnology sector for investors. Despite of the innate appeal of the idea of using cancer vaccines as an effective weapon against cancer, the results of late stage human clinical trials have been discouraging to scientists, entrepreneurs and investors.
Success with Checkpoint Inhibitors Brings New Life to Immunotherapy Approach. The introduction of novel medicines known as checkpoint inhibitors for the treatment of cancer has changed views among investors over the future of immunotherapy. The medical hypothesis claiming that the immune system can defeat cancer have gotten a new life. In 2017, Bristol-Myers Squibb (BMS) and Merck & Co. had blockbuster annual sales of their respective checkpoint inhibitors, Opdivo and Keytruda. BMS’s F2017 sales of Opdivo were $4.95 billion, whereas sales of Keytruda by Merck were $3.8 billion. In 2017, U.S. FDA approved Novartis’s Kymriah and Gilead’s Yescarta, two novel immunotherapies for the treatment of blood cancer. These recent developments have brought to the investment community a new wave of enthusiasm, based on the prospects for emerging biotechnology companies committed to developing novel immunotherapies for the treatment of cancer.
IMV, Inc. (Nasdaq: IMV, Market Cap $247 mm) is developing DPX-Survivac, a novel immunotherapy approach, in combination with checkpoint inhibitors from Incyte (Nasdaq: INCY) and Merck & Co. Bavarian Nordic is still developing Prostvac, in combination with checkpoint inhibitors, for the treatment of prostate cancer. Despite of recent setbacks, Bavarian is collaborating with the National Cancer Institute (NCI). Prostvac targets the prostate specific antigen (PSA). The vaccine is designed to stimulate an anti-tumor immune response against prostate cancer cells. Bullish investors believe that positive results from the seven ongoing clinical trials evaluating Prostvac in combination with checkpoint inhibitors could have a positive impact on sentiment, potentially driving the valuation of the company higher, as well as other stocks in the sector.
Cancer Patient are Immuno-Compromised – Vaccines Will Not Work. Cancer vaccines are designed to harness the power of the immune system to fight cancer. However, the immune system of a cancer patient is depressed, the tumor microenvironment generates various signals and pathways resulting in a state known as immune-compromised. The opposite, in normalcy, is a fully capable immune system or immune-competent state. Most vaccines are designed to work in immune-competent patients, but this is not the case in cancer patients.
Ten years ago, cancer company Cell Genesys halted all clinical development efforts with GVAX, layoff the majority of its staff, after the drug failed in a Phase III prostate cancer trial. The news sparked significant skepticism, as investors dealt with a subsequent string of clinical failures in the cancer vaccine area. Merck KGaA’s Theratope and Bavarian Nordisk’s Prostvac also failed in late stage clinical development. Merck KGaA failed twice in Phase III clinical trials, first with Theratope in breast cancer in 2003, and then with Stimuvax in lung cancer in 2012. In 2015, Bavarian Nordic had partnered with Bristol-Myers Squibb (BMS) to develop Prostvac for the treatment of prostate cancer. Last year, the company discontinued Phase III clinical trials. The news triggered a selloff on the stock, which declined 50% after the press release came out. Bavarian will not receive up to $1 billion in milestone payments, which were tied to the partnership deal signed with BMS in 2015.
Investors in Dendreon remember very well their frustrations. Dendreon’s stock languished in the doldrums, even after the U.S. FDA cleared the company’s prostate cancer vaccine, Provenge, for commercialization in 2010. The high level of complexity of Provenge, difficult manufacturing process, led to significant challenges for Dendreon, which the company was never able to overcome. With a price tag of $93,000 for annual treatment per patient, facing emerging competition, Provenge sales were disappointing. Dendreon’s stock tanked, triggering a death spiral leading to Dendreon’s bankruptcy. In spite of being touted as a blockbuster drug (with estimated potential sales of more than $1 billion), Provenge was later sold to Valeant Pharmaceuticals for only $415 million (purchase included other assets of the bankrupt Dendreon Corporation). On October 12, 2018, shares of Immune Design Corp. (Nasdaq: IMDZ, Market Cap $69 mm) lost 42% of their value after the company discontinued its CMB305 cancer vaccine program. All these negative developments have spooked out a group of investors, who did abandon the sector. Even to this day, there are investors in the bearish camp who remain reluctant to even look at potential investments in the cancer vaccine area.
Newly and Innovative Designs, The Future of Cancer Vaccine Field. Ignoring the deep negative sentiment among investors in bearish camp, while putting aside the overly optimistic view of investors in bullish camp, the prevailing view of industry experts is that the search for an efficacious cancer vaccine will continue. However, resurgence will likely be driven by new vaccine designs and innovation. Several companies including: Neon Therapeutics, Inc. (Nasdaq: NTGN, Market Cap $170 mm), Gritstone Oncology, Inc. (Nasdaq: GRTS, Market Cap $485 mm), Advaxis (Nasdaq: ADXS, Market Cap $43 mm), Agenus (Nasdaq:AGEN, Market Cap $197 mm), Nant and Moderna (both private companies planning IPOs) are developing novel cancer vaccines based on a new scientific concept, cancer neoepitopes.
What is a neoepitope? Mutations in cancer cells give rise to new DNA sequences (known as neoepitopes) which are exclusively present in these cells. Normal cells do not contain these newly generated DNA sequences. As a result, cancer neoepitope vaccines are designed to direct the anti-tumoral immune response to target these specific sequences only present in cancer cells, while sparing normal cells (Nature Reviews Drug Discovery 2016(15)p663-665).
Some experts believe that vaccines designed to target multiple tumor antigens at once, rather than exclusively targeting neoepitopes, will become the solution. Dr. Bernard Fox, CEO of Ubivac, believes that its new vaccine, Dribble, which targets multiple key tumor antigens at once, could be potentially an effective drug to use in combination with checkpoint inhibitors. Ubivac is a private biotechnology company based in Oregon, Washington, which collaborates with the Providence Cancer Center.
Dr. Bernard Fox is a prestigious immunologist. He has served/serves on the Board of Directors of AstraZeneca, Bristol-Myers Squibb, EMD Serono, Janssen/Johnson & Johnson, Novartis, Perkin Elmer and Pfizer. Dr. Fox is the chief of the Laboratory of Molecular and Tumor Immunology at the Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center. Dr. Fox is also a professor of molecular microbiology and immunology at Oregon Health and Science University. Dr. Fox was an investigator in the first trial of gene-modified tumor vaccines in Oregon. In 2015, Dr. Fox received the Visionary/Legacy Award from the Society for Immunotherapy of Cancer.
Cancer Vaccines Used in Immunotherapy Combination. Dr. Fox believes that current efficacy of immunotherapy treatments, which show efficacy in 30-40% of patients, could be improved to 90% of patients in the future. He is a true believer that the use of cancer vaccines in combination with checkpoint inhibitors is the solution. Dr. Fox is leading its team at Ubivac to develop “Dribble”, which is currently in Phase I/II human clinical trials. He believes that the solution does not consist of turning on just T-lymphocytes, but rather triggering a total anti-cancer immune response (including B-lymphocytes secreting antibodies, as well as T-cells), involving all arms of the immune system to bombard the tumor with multiple weapons, and prevents its escape or immunosuppression pathways, which have been the major hurdle in cancer immunotherapy.
The following video illustrates the principles behind Ubivac’s cancer vaccine technology.
The Providence Cancer Center, as well as cancer patients treated at the center, have hopes that immunotherapy studies could bring to fruition novel treatments to prolong patient survival, eventually leading to the development of a potential cure for the disease.
- Immunotherapy: Revolutionizing Cancer Treatment since 1891
- Don’t Get Burned By The Next Cell Genesys
- Therapeutic cancer vaccine survives
biotech bust. Pharmaceutical company rescues landmark prostate-cancer
- Theratope Phase III results deliver blow
to Merck KGaA and Biomira
- Oncothyreon routed after Merck KGaA's
Stimuvax flops in PhIII lung cancer trial
- Bavarian Nordic tanks after
Bristol-Myers-partnered vaccine flunks phase 3 prostate cancer trial
- Cancer Vaccines, long considered
failures, are hot again
- Cancer in the Crosshairs: IMV Looks to
Deliver Immunotherapy a New Way
- Immuno-oncology player Neon Therapeutics
looks for $115M in IPO
- Immuno-Oncology Players Gritstone And
Sutro Join The Biotech IPO Frenzy
- Advaxis cuts staff as it seeks partner
for troubled cancer vaccine
- Agenus sells cut of Incyte, Merck
- Cancer vaccine company Nant getting
ready to go public
- Is Moderna prepping for biotech's
- Immune Design's stock plummets toward
record low after cancer vaccine program discontinued
- The cancer vaccine resurgence (Nature Reviews Drug Discovery 2016(15)p663-665)
- Bernard Fox, Ph.D., the promise of
Immunotherapy in curing cancer
- Ubivac’s technology
Photography credit: pixabay.com