2023-10-14 03:32:21 ET
Summary
- TScan Therapeutics is developing TCR T-cell therapies for cancer using a transposon-based T cell engineering method.
- The company aims to target a broader patient population by addressing a wide range of human leukocyte antigen (HLA) types.
- TScan has a partnership with Amgen and has a sufficient cash balance to last for 6-7 quarters.
TScan Therapeutics ( TCRX ) is a developer of TCR T-cell therapies targeting cancer. The company used a transposon-based T cell engineering that offers advantages over other methods, like viral-based gene delivery systems. It can provide greater flexibility in terms of the size and complexity of the genetic cargo that can be introduced into T cells and has a lower risk of causing insertional mutagenesis (unwanted mutations in the host cell's DNA). As a result, this technique has gained attention in the development of CAR T cell therapies and TCR-engineered T cell therapies for various diseases, particularly cancer.
The company’s pipeline looks like this:
That looks like an impressive pipeline until you notice that phase 1 is all they have got for all their most advanced programs. I believe this is throwing a lot of stones at the birds, sans aiming, to see which will hit the mark. The problem with such an approach - as against a stone or two with proper aim - is that none may hit their marks. Interestingly, they have programs in all sorts of cancer tumors, and even an Amgen-partnered program in Crohn’s Disease, an autoimmune disease.
TScan Therapeutics aims to target a broader patient population by addressing a wide range of human leukocyte antigen (HLA) types. HLA is a group of proteins found on the surface of cells that play a crucial role in the immune system. HLAs are responsible for presenting antigens to T cells. Each individual has a unique set of HLA proteins, which can make it challenging to develop therapies that work for a broad patient population.
One of the challenges in the development of TCR-T therapies is the diversity of HLA types across different individuals. Tumor antigens are often presented by specific HLA molecules. Therefore, TCR-T therapies developed for one HLA type may not be effective for individuals with a different HLA type. TScan's approach appears to involve targeting a broader range of HLAs, allowing their TCR-T therapies to be effective in a larger portion of the patient population.
In humans, the human leukocyte antigen (HLA) system is highly diverse and consists of three major classes: HLA class I, HLA class II, and HLA class III. Each class plays a specific role in the immune system. Regarding HLA class I alleles, humans typically inherit two sets of HLA class I genes (one from each parent), and within each set, there are typically six HLA class I alleles. These alleles are usually denoted as HLA-A, HLA-B, and HLA-C. A and B are responsible for presenting endogenous antigens (peptides from within the cell) to cytotoxic CD8+ T cells. ~90% of people in the U.S. are positive for at least one of these top 6 HLA types. The difference between TScan and other TCR therapies is that unlike most TCR-T therapies that target one HLA (up to 40% of people), TScan is working to target the top 6-8 HLAs (~90% of people).
In heme malignancies, TScan designs programs to prevent relapse in patients undergoing HCT. Lead programs TSC-100/101 are designed to prevent relapse by eliminating cancer cells remaining after HCT, considered the standard of care in non-B cell malignancies. A multi arm phase 1 trial is now enrolling patients in the final dose level.
In solid tumors, TScan once had a $48mn deal with Novartis to develop therapies for kidney cancer. Today, it says it exploits the natural propensity of TCRs to recognize specific antigens, such as proteins or peptides, presented by human leukocyte antigens (HLAs). These TCRs are isolated and their antigen-recognition capacity enhanced, which TScan is utilizing to create an ImmunoBank of customizable TCR therapies for individual patients and cancer types.
TScan also has a multi-year partnership with Amgen for “TargetScan to identify targets recognized by CD4+ T cells in patients with Crohn’s disease; option to expand collaboration in ulcerative colitis.” This includes a $30mn upfront payment and a $500mn milestone payment option. It includes one HLA target and option to include one more HLA target for additional payments.
Financials
TCRX has a market cap of $169mn and a cash balance of $208mn. In the previous quarter, the company completed an offering of $135mn. Research and development expenses for the second quarter ended June 30, 2023, were $21.2 million, while general and administrative expenses for the second quarter ended June 30, 2023, were $6.5 million. At that rate, the company has enough cash to last them for 6-7 quarters.
The company is primarily owned by hedge funds and VC firms at 50%, followed by the retail public at a healthy 31%. Key holders are LYNX1 Capital, ECOR1 Capital and Biotechnology Value Fund.
Risks
The reason for the lack of coverage of this stock on Seeking Alpha, as well as the low market interest as demonstrated by a market cap lower than its cash reserve, seems to be that despite many years of existence, I believe that the company does not have any real data to support its programs. Basically, it has no proof of concept, and without that proof, it is just talk. They have some phase 1 data which mainly consists of RP2D dosing finalization, however there does not appear to be any efficacy related data. There is some validation of mechanism of action in the form of donor chimerism, but whether this is full chimerism or mixed, and what are the numbers etc have not been disclosed. All told, the company is progressing agonizingly slowly, which is the single cause of lack of any sort of market enthusiasm.
Trading volume is also very low, reflecting that lackluster enthusiasm. It will be difficult for investors to buy or sell this stock as needed.
The principal risk with TCRX is that despite being in the market for a few years, they still have not produced a single proof of concept data from a randomized clinical trial. They have an impressive looking pipeline, however without data, this pipeline has no value at all.
Bottomline
There’s not much here except the Amgen deal which happened in May. $30mn in upfront fees is not a trifling matter for a company like TCRX, even if it is pocket change for Amgen. Other than this, there does not seem to be much of interest in TCRX at this time. I would have said “I will avoid” and left it at that, but because we assume Amgen does its due diligence better than us, we will just say “I will wait for further data” before taking a call.
For further details see:
TScan Therapeutics: That Recent Amgen Deal Is The Only Point Of Interest