What’s cooking at Talem Therapeutics?
A very warm welcome, reader, to our next blog!
Global attention toward finding solutions to prevent SARS-COV-2 infections and to treat COVID-19 is without a doubt justified. Talem Therapeutics has continued to work diligently to develop a solution. The company frequently reported on the development of its PolyTope® TATX‑03 antibody cocktail to prevent and treat COVID‑19 and will remain doing so. But this innovative biotech enterprise is so much more than “COVID‑19” alone. Talem is also involved in designing smart therapies for various cancers, neurological and neurodegenerative disorders, autoimmune and cardiovascular diseases. We are excited to share more about our development of other thrilling therapies for a wide variety of indications.
Cancer can affect everyone regardless of gender, age or social status. One of the greatest research tasks in the scientific world is to bring effective solutions to this harmful disease, which is a tremendous burden not only for the suffering individuals but for their families and for the society at large as well. If no further action is taken, the number of people newly diagnosed with cancer annually worldwide will increase from 14 million in 2012 to 24 million by 2035 (Pilleron et al., 2018). Many organizations have recognized this emergency and took action to improve the prospects for cancer patients. Over the last years, much effort and progress has been made in comprehending malignancies, prevention, early recognition and diagnosis, and treatment.
Prominent researchers predict that by 2033 all cancers will have become chronic ailments, rather than a terminal illness (Boutsma, 2018). There are important scientific breakthroughs on which these scientists based their opinion. The first important breakthrough was at the start of this century when the human genome was unraveled, and it became possible to compare the (active) genes in diseased and healthy cells. These comparisons delivered a huge amount of information valuable for understanding how to stop and clear malignancies.
Another important scientific breakthrough is the availability of immunotherapies to treat cancer. Their availability turns medical doctors into tumor torpedos using medicines aiming accurately at the tumor. The doctors are thus less and less forced to use a cannon, which chemotherapeutics actually are, killing fast dividing cells, diseased or healthy.
Although there are different approaches to immunotherapy, Talem has invested in developing a variety of dedicated antibodies to be used as immunotherapy. The company has found a satisfying mission in developing programs to tackle this destructive disease.
Figure 1. Mechanisms of action of TATX-112 anti-TrkB antibodies. The antibody-drug conjugate (ADC) is like a Trojan horse entering the diseased cell to kill it (left side). Alternatively, the antibodies may prevent activation of the TrkB receptor, and thus prevent cancer cell growth, invasiveness, survival, metastatic behavior and suppression of chemotherapeutic sensitivity, by hindering the binding of its BDNF ligand (right side).
One of Talem’s leading campaigns is on developing antibodies targeting tropomyosin receptor kinase type B (TrkB), which is overexpressed in many solid tumors, including breast, lung and colon-rectum tumors. The protein sitting in the membrane of malignant cells contributes to their growth, survival, invasiveness, and metastatic behavior. In addition, this TrkB receptor suppresses the chemotherapeutic sensitivity of the tumor cells. Talem’s discovered antibodies (TATX-112) interfere with TrkB’s undesired actions and is an attractive approach to reduce tumor growth. One of the most electrifying potentials of these TATX-112 antibodies is that they act as a Trojan horse by weaponizing them with a cytotoxic compound that is able to specifically kill the ‘bad cells’ (see left side in Figure 1).
Besides TrkB, other oncological targets for our antibodies in our impressive pipeline aim at:
stopping deterioration of B-cells (TATX-114 antibodies);
halting recruitment of macrophages defending tumors (TATX-22 antibodies);
ending tumor cell adaptation (TATX-20 antibodies);
suppression of tumor infiltrating regulatory T-cells (TATX-116 antibodies);
T-cell activation to facilitate selective tumor cell destruction (TATX-24 antibodies).
We will continue to report about these anti-cancer therapeutic developments through the different channels we use to inform you about what is cooking in Talem’s kitchen!
Although already a major task, Talem is doing much more than helping healthcare systems to transform cancer into, at most, a chronic disease. There are other exciting developments for other indication areas to tell you about and we want to give you a glimpse of these other products in Talem’s pipeline.
Atherosclerosis is one of the other wide-reaching common causes of morbidity and mortality. Atherosclerosis is a sneaky ‘assassin’, as the affected person only notice severe narrowing of arteries and obstruction of the blood flow when hit by a stroke or heart attack. The narrowing is the buildup of plaque by several substances, of which low-density lipoprotein (LDL) is one of the major substances, in the inner lining of an artery. Transport of this ‘bad’ cholesterol over the endothelial cell of the artery from the blood flow side to the opposite side in the subendothelial space contributes to this accumulation. How fantastic would it be when we could hinder this transport and thus preventing the deadly accumulation without interfering any other biochemical processes in our body?
Our target to accomplish this is a cell membrane-bound protein restricted to endothelial cells, activin-like kinase 1 (ALK‑1), of which its low-affinity but high-capacity for binding LDL has been discovered relatively recently (see Figure 2). Fortunately, ALK‑1’s LDL-binding site is independent of its site regulating its main function. In other words, blocking of the LDL-binding site is an attractive therapeutic approach and that is exactly what Talem’s TATX-21 antibody is doing!
Figure 2. Blockage of transcytosis of LDL by TATX-21 antibodies. From early age on, ‘bad cholesterol’ (LDL and variants) is transported from the blood flow over endothelial cells to accumulate in the subendothelial space (left side) where this buildup starts to narrow arteries. The TATX-21 antibodies are able to inhibit this uptake of LDL and consequently prevent atherosclerosis.
We mentioned the discovery of anti-TrkB TATX‑112 antibodies here above for tumor treatment, but actually, these antibodies are of great interest to treat neurological and neurodegenerative conditions as well. Likewise, the TATX-114 antibodies may also be developed to relieve autoimmune diseases and suppress inflammatory reactions. It will still take a lot of effort and time to bring these indications to the clinic, but we have an antibody repertoire ready to start that journey.
You may conclude that Talem has many pans on the stove and that the contents of some of these pans start to boil now. Wonderful dishes are about to be served. Do you feel our excitement about what is happing in our kitchen?
REFERENCES
Boutsma (2018) Targeted therapy is becoming the norm for treating tumours, C2W International. https://c2winternational.nl/2018-03/targeted-therapy-is-becoming-the-norm-for-treating-tumours/ (last visited March 31, 2022)
Pilleron S, Sarfati D, Janssen-Heijnen M et al. (2019) Global cancer incidence in older adults, 2012 and 2035: A population-based study. Int J Cancer 144, 49-58. Doi: 10.1002/ijc.31664