YB1 oncolytic bacteria: solving technical pain points and grasping development trends

According to the most widespread accounts, the term cancer was first coined by Hippocrates, the ancient Greek physician who was the “father of medicine” in the West, and if the birth of the word “cancer” is seen as the beginning of humanity’s formal confrontation with this disease, then cancer has been haunting It has plagued humanity for more than 2000 years.

In the past 20 centuries, human ingenuity has reshaped the ancient pattern of our one-way passivity in life and health through the intergenerational development of biotechnology. We have overcome many complex diseases that could not be overcome in the past.

However, cancer has not yet been fully cured. So what is it about cancer that makes it so difficult to cure?

Infinite proliferation + metastasis = cancer cells master “superpowers”

All normal cells in the body follow the natural process of “growth-differentiation-death,” with new cells being created and old cells dying so that the total number of cells in an average human body is constant. Although cancer cells are derived from normal cells in the body, they upset this balance because they have two superpowers.

One is the ability to proliferate indefinitely. While normal cells are controlled by an upper limit on the number of divisions, cancer cells are entirely free from restraint due to genetic mutations and can proliferate without limit and freely, making them challenging to eliminate.

The second is the ability to invade and metastasize. The invasive ability of cancer cells also stems from their solid proliferative capacity. It is called infiltration because the cancer cells continue to multiply and thus invade the surrounding tissues. In the case of cancers of the digestive tract, for example, colon cancer that occurs in the mucosa will slowly infiltrate the submucosa, the muscular layer, and even the plasma layer. When the tumour invades the muscular and plasma layers, the prognosis becomes worse.

At the same time, tumours need to draw nutrients from the blood when they grow, and they may even create their blood vessels to connect with the body’s existing blood vessels. With this connection, some cancer cells may flow through the blood circulation to various tissues throughout the body, such as the liver, brain, and spine, waiting for an opportunity to form new tumour lesions. It is known as distant metastasis.

Although cancer may have been around for 2,000 years, it is only in the last couple of hundred years that humanity has “fought” cancer (or been able to fight it). Traditionally, cancer has been treated in three ways: surgery, radiotherapy, and chemotherapy, all of which are still in use today but are not as effective as they could be, and the pain points of conventional cancer treatment are still waiting to be addressed.

How to solve the traditional cancer treatment pain points?

Now, it can be said that the main challenge in treating cancer is the issue of targeting.

Cancer cells are mutations of the patient’s normal cells and, therefore, very similar to the patient’s cells. Cancer cells can both invade nearby tissues and spread further into the body, and in order to treat cancer, effective treatments must distinguish between cancer cells and healthy cells.

The issue of targeting primarily limits traditional cancer treatments. For example, surgery can remove tumours directly and is effective for early-stage cancers; However, once cancer has spread to different locations in the body, the effectiveness of surgery is limited. Radiation therapy can kill tumour cells and shrink them by exposing them to a beam of radiation, but like surgery, the effectiveness of radiation therapy is significantly reduced once cancer has spread.

Recent advances in genetics and cell biology have opened the way for several potential new therapies that could target cancer cells more precisely while causing minor damage to normal cells.

For example, targeted molecular therapies inhibit the growth of cancer cells by acting on specific targeted molecules associated with the proliferation and survival of tumour cells, On the other hand, immunotherapy uses antibodies to bind to tumor antigens expressed on the surface of cancer cells, enabling the body’s immune system to recognize and eliminate these cancer cells. In addition, some of the current emerging combination therapies seek to combine more than one therapy to produce synergistic anti-tumor effects.

On the other hand, immunotherapy uses antibodies to bind to tumour antigens expressed on the surface of cancer cells, enabling the body’s immune system to recognise and eliminate these cancer cells. As well as some of the current emerging combination therapies seek to combine more than one therapy to produce synergistic anti-tumour effects.

Combination therapies containing immune checkpoint inhibitors are expected to improve the response rate and tolerability of inhibitor monotherapies, potentially improving the efficacy of approved indications and cancer types for which there is currently no effective treatment.

Publicly available information documents that the FDA has approved multiple combination therapies since 2015. Based on clinical trial data, Ipilimumab combined with Nivolumab has received FDA breakthrough approval regarding advanced hepatocellular carcinoma. Given the recent success, the combination of anti-PD-1 and anti-CTLA-4mAbs has more significant potential than PD-1 monotherapy. As technology improves, anti-CTLA-4mAbs are expected to show greater efficacy in more indications and are expected to show great potential in combination with other immuno-oncology therapies (not limited to PD-1 combination therapies).

Thus, while the mainstream treatment paradigm in cancer therapy has evolved over the past decade, more cutting-edge innovative therapies have emerged with increasing intensity, from targeted therapy to immunotherapy, to the combination of targeted therapy and immunotherapy. More and more innovative research ideas have brought new hope to address traditional cancer treatment pain points from cell therapy to lysing viruses to lysing bacteria.

The concentration of innovative therapies brings new hope，YB1 pioneers immunotherapy with oncolytic bacteria

At the same time, the global oncology drug market has achieved continued rapid growth in scale, attracting more companies in the biotechnology sector to enter the market in the hope of taking advantage of the enormous market roundup in the future.

HKND Limited, which has successfully developed the world’s first oncolytic bacterial vector product YB1, has gained widespread attention from the industry market for its breakthrough in researching innovative cancer immunotherapy — oncolytic bacterial therapy.

The core technology product of HKND, YB1, is a genetically programmed strain of Salmonella typhimurium, which can be used as a vector to deliver antibodies, mRNA, protein drugs, etc., precisely targeting the hypoxic region inside the tumour and replicating and amplifying in large quantities inside the tumour. which can significantly increase the concentration of YB1 vector at the target location of solid tumours and release a variety of therapeutic “warhead” drugs. The YB1 vector can significantly increase the concentration of YB1 at the target site of solid tumors and release a variety of therapeutic “warhead” drugs to inhibit tumor growth and cause tumor oncolytic while eliminating tumor metastasis, which has significant clinical potential.

YB1 is tumour-targeted using the world’s first tumour hypoxia-specific targeting technology and has the only patent in the world for oxygen-regulated tumour-loving bacteria.

YB1 technology is also highly compatible with chemotherapeutic agents, immune checkpoint antibodies, and cellular technologies such as CAR-T. The company currently has a pipeline of seven innovative products for oncolytic bacteria in combination with other drugs In addition to oncology applications, YB1 technology can also be used to treat various thrombotic diseases, and the company currently has three thrombooncolytic-related product pipelines in place.

Industry outlook: future trends in the oncology drugs market

Grasping the industry’s future trends is an essential skill for every industry player to stand firm and achieve sustainable development. The following are some of the most widely recognised trends in the global oncology drugs market at this stage.

Firstly, cancer is moving towards chronic disease management. In the future, cancer will be seen as a chronic disease similar to diabetes and hypertension. Cancer requires in-hospital treatment and subsequent out-of-hospital rehabilitation, monitoring, and maintenance. Therefore, there is a growing demand for more convenient and effective treatments such as subcutaneous injections that are easier to administer, take less time, and are more quickly absorbed by patients than other injections.

Secondly, expanding combination therapies are gaining wider recognition. It is foreseeable that combination therapies in the anti-tumor field will become a trend as they will lead to greater therapeutic efficacy, which points to the future direction of cancer therapies globally and in China. Clinical studies have shown that the combination of PD-1/PD-L1 antibodies with chemotherapy, targeted therapies (including VEGF pathway inhibitors), or other immunotherapies can significantly improve the efficacy.

Thirdly, precision therapy has become a development trend. With the development of gene sequencing technology and the improvement of detection efficiency and identification of biomarkers (which indicates new scope for the development of tumour therapy), specific immunotherapy can be administered according to the patient’s tumour status. Biomarker-based pan-tumor species are becoming possible, leading to increased remission rates and hopefully improved survival of cancer patients, providing a favorable environment and conditions for precision therapy.

Then there is the growing size of the out-of-hospital market for oncology drugs. Publicly available information shows that the out-of-hospital market for oncology drugs is expanding. In 2016, the revenue from out-of-hospital sales of oncology drugs in China accounted for 6.6% of the total oncology drugs market. A percentage increases to 15.6% in 2020 and is expected to increase to 39.8% and 55.5% in 2025 and 2030, respectively.

In addition, the expanding indications for cancer immunotherapy, the continued emergence of new and innovative therapies, and the increasing affordability of high-priced innovative drugs are all future trends in the oncology treatment field. Biotechnology companies that have been scrambling to enter the market in recent years are expected to continue to compete in this famous track and inject new momentum into the industry’s long-term development.