tiratus phaesuwan/iStock via Getty Images
tiratus phaesuwan/iStock via Getty Images
Adicet Bio, Inc. (NASDAQ:ACET) is expecting to provide clinical updates for two of its key programs in the 2nd half of 2024. It received IND clearance to begin testing its CAR-T known as ADI-001 in a phase 1 study for the treatment of patients with lupus nephritis [LN]. Even though this study is not expected to begin until Q2 of 2024, it is expected that it will be able to provide a data update for this specific program in the 2nd half of 2024. The significance of this is that should ADI-001 prove to work in treating patients with lupus nephritis, then it might be able to target other autoimmune disorders. What makes this biotech great is that its targeting of CD20 using this CAR-T is highly versatile.
In essence, it can also be used to treat patients with cancers as well. Speaking of which, it is also being explored in a phase 1 study, known as GLEAN for the treatment of patients with mantle cell lymphoma [MCL]. This is a solid program to move forward with, because early clinical data revealed thus far was shown that MCL patients fared very well when given this treatment. That is, this CAR-T established high percentage response rates in patients with late-line MCL. The goal is to possibly advance this program forward in a pivotal study, which might ultimately be used to obtain Accelerated Approval. Regardless, a clinical update on this program is expected in the 2nd half of 2024.
The main clinical program in Adicet's pipeline would be the use of CAR-T ADI-001, which is being used to treat patients with mantle cell lymphoma [MCL]. The use of this treatment was explored in the phase 1 open-label GLEAN study, which enrolled adults diagnosed with B-cell malignancies who have either relapsed or are refractory to two prior regimens. The mantle cell lymphoma therapeutics market is expected to reach $3.04 billion by 2027. While the goal was to test out all Non-Hodgkin Lymphoma patient populations using ADI-001, the best possible results were obtained for late-line patients with MCL. Why was this the case? That's because of the high response rates I noted above in the beginning of this article. Such positive data from this phase 1 GLEAN study was reported in June of 2023. Late-line MCL patients given ADI-001 were said to have achieved an 80% complete response [CR] rate and a 60% 6-month CR rate. With this data on hand, Adicet believes that its best course of action is to move forward targeting this specific MCL patient population. Where this company might do well in the cell therapy space is that it is developing this CAR-T as an allogenic off-the-shelf type of a treatment option. Not only were such high response rates achieved in this early-stage study but the safety profile was very good as well. There was no risk of cytokine release syndrome [CRS], immune effector cell associated neurotoxicity syndrome or T-cell malignancies. With this highly positive data in late-line MCL patients, the goal is to advance a pivotal study under an Accelerated Approval pathway. With respect to a catalyst for this program, it is expected that Adicet will provide a clinical update for ADI-001 for MCL in the 2nd half of 2024.
Adicet Bio has a good chance at being able to target this MCL patient population and take a good chunk of market share. That's because there is one drug known as brexucabtagene autoleucel given Accelerated Approval for the treatment of patients with relapsed/refractory MCL. Such a therapy, which comes from Gilead Sciences, Inc. (GILD), is a CD-19 directed CAR-T approved for this patient population. There are two advantages that Adicet's ADI-001 might be able to achieve, which will provide competitive advantages for these patients. The first of such a competitive advantage would be off-the shelf dosing, being that it is a CD20 allogeneic CAR-T, which is targeting these MCL patients. This would mean an improved ability to quickly manufacture the necessary supply for clinical development. The second competitive advantage would be the potential for longer duration of response. That's because it was shown to have an improved Cmax exposure and 28 day persistence, compared to approved CD19 Autologous CAR-Ts being used. The third and final competitive advantage would be in terms of safety. That is, treatment with ADI-001 was shown to have no significant risk of causing cytokine release syndrome [CRS], ICANS or T-cell malignancies. All of these are major risk factors seen with autologous CAR-Ts. ICANS is a major issue, whereby it is a neuropsychiatric syndrome observed in days to weeks after patients are given an immunotherapy such as with CD19-directed CAR-T. It stands for "Immune Effector Cell-Associated Neurotoxicity Syndrome. With these advantages, along with the CR rate and 6-month CR Rate achieved to date, it has a good shot at taking a large chunk of the market share from Gilead Science's brexucabtagene autoleucel, along with other autologous CD-19 directed CAR-Ts.
A good thing about Adicet's Bio advancement of ADI-001 is that it is not only good for targeting patients with certain types of cancers. That is, it can also be developed to treat patients with autoimmune disorders. One such autoimmune disorder being looked at is lupus nephritis. Lupus is a disorder whereby a person's immune system attacks their own tissues and organs. With respect to lupus nephritis, this occurs when the disorder targets the kidneys. Specifically, the part of the kidneys responsible for filtering out waste. This is another large market opportunity for Adicet Bio to go after a well. It is expected that the global lupus nephritis treatment market is expected to reach $5.67 billion by 2033. This is another program which has made great clinical progress in the clinic. Especially, since an IND application was cleared by the FDA back in December of 2023. With such regulatory clearance received, the biotech is on track to begin a phase 1 study, using ADI-001 for the treatment of patients with LN, in Q2 of 2024. Investors won't have to wait long to see clinical data from this program either. It is anticipated that a clinical update from this phase 1 study could be released by the 2nd half of 2024.
In terms of Lupus Nephritis [LN], there are two competitors that might have to go against. One such drug is known as BENLYSTA [belimumab], which is an approved biological monoclonal antibody for the treatment of systemic lupus erythematosus [SLE]. It is designed to decrease the amount of circulating B-cells and prevents the production of autoantibodies that form as well. This biologic agent comes from GSK plc (GSK) and has been proven to improve complete renal response in patients with lupus nephritis [LN]. The downside is that BENLYSTA must be given alongside with a patient's current standard of care [SOC] medication. Another drug for LN, which Adicet Bio might have to compete against would be LUPKYNIS [voclosporin], which was approved by the FDA for the treatment of patients with LN. LUPKYNIS works in a different manner, in that it acts on T-cells. That is, it suppresses T-cells from causing injury to a patient's kidney. A thing to note about this drug is that it is given in combination with background immunosuppression. Where Adicet Bio's ADI-001 might achieve a competitive advantage in might be with respect to several factors. For starters, it could have innate and adaptive immune targeting capability. This could allow it to achieve better responses for patients, but of course this remains to be seen. A second item could be in terms of the drug being capable of being given alone, with no need for immunosuppression or other background therapies. A possible third competitive advantage could also end up being better safety outcome. The phase 1 trial is expected to start in Q1 of 2024. This could end up being another promising program for this biotech.
According to the 10-Q SEC Filing, Adicet Bio had cash and cash equivalents of $183.3 million as of September 30th of 2023. The company has been able to maintain the cash it has because of an ATM agreement it first made back in March of 2021 with JonesTrading Institutional Services LLC. This was whereby the company could offer and sell up to an aggregate amount of $75 million of shares of common stock from time to time. In August of 2022, it decided to use this ATM and sold 2,611,723 shares of its common stock at a price of $17.23 per share.
This resulted in net proceeds of about 43.4 million to it, after deducting sales agent commissions. This prospectus ATM agreement was updated with a supplement one, with the offer for the sale of up to $100 million shares of its common stock from time to time, which includes $30 million of shares of common stock not used in the prior one and up to an additional $70 million of shares of common stock. No shares of stock have been sold yet under this ATM program, but should Adicet need to raise additional cash to fund its operations, then this is a financial instrument it could utilize in 2024.
There are several risks that investors should be aware of before investing in Adicet Bio. The first risk to consider would be with respect to the phase 1 GLEAN study, which is using ADI-001 for the treatment of patients with late-line mantle cell lymphoma [MCL]. Even though this CAR-t was able to generate an 80% CR rate and a 60% 6-month CR rate, there is no assurance that the updated data will turn out to be similar or superior. A second risk to consider would be the regulatory front of ADI-001 for MCL. Why is that? That's because the goal is to initiate a pivotal study to be used for Accelerated Approval.
There is no assurance that the FDA will allow the company to initiate a pivotal study for this program, nor that such a trial could ultimately be used to file for Accelerated Approval. It's highly possible that the FDA may end up requiring a more robust study, this is a risk to consider with biotechs seeking such a pathway. A third risk to consider would be in terms of the advancement of ADI-001 for the treatment of patients with lupus nephritis [LN]. Even though this CAR-T was shown to work well in treating patients with cancer [specifically mantle cell lymphoma], there is no guarantee that it will do just as well in being able to treat patients with LN. This brings up the fourth and final risk to consider as well, which is that it remains to be seen if ADI-001 can eventually be used to target other autoimmune disorders.
Adicet Bio has been able to make extensive progress in being able to move its pipeline forward. It has been able to achieve high response rates from its phase 1 GLEAN study, using ADI-001 for the treatment of patients with late-line mantle cell lymphoma [MCL]. Not only that, but investors can look for a major update about this specific program in the 2nd half of 2024. Besides this as a major catalyst this year, there is another one to look forward to. This would be a first look into whether or not ADI-001 can be used to treat patients with autoimmune disorders as well. This remains to be seen, but things will kick off with trial initiation in Q2 of 2024.
From there, it is expected that an update of ADI-001 for the treatment of patients with lupus nephritis, will be released in the 2nd half of 2024. With positive phase 1 data targeting late-line MCL patients, plus a few catalysts during this year, I believe that investors might be able to capitalize on any potential gains made. The last thing to note is that progress is being made to target other types of cancers with CAR-Ts. For instance, an IND to begin testing of ADI-270 in a phase 1 study for the treatment of patients with renal cell carcinoma [kidney cancer], is expected in Q2 of 2024.