Recently, ORIC Pharmaceuticals announced its Q2 2025 financial report. More importantly, it decided to enact a huge change to its pipeline, which was to put emphasis on its two lead candidates: ORIC-944 as a PRC2 inhibitor to treat patients with metastatic castration-resistant prostate cancer and then Enozertinib (known previously as ORIC-114) for the treatment of patients with lung cancer. The reason why it chose to go this route is likely because it will be able to conserve cash and make sure it has enough to fund both of the phase 3 studies it intends to run for these indications. In order to accomplish this move, it had to take two measures as part of this pipeline reprioritization change.
The first item on the list was that it had to reduce its staff, and so it decided to reduce its workforce by 20% to save funds. Another move it made was to wind down research activities, which involved reducing or removing research program candidates from its pipeline. All is not lost with this last move, though, because even if it is not going to fund any of these other preclinical candidates, it mentioned in its earnings release that it will still attempt to find partners who have the cash that are willing to fund them if possible. While reducing pipeline candidates is never a good thing, there was a huge positive to come about from it, which was that it will extend its cash for a long period of time.
As a matter of fact, it expects its cash to help fund its operations into the 2nd half of 2028. Not only does this mean that it won’t need to raise additional cash for an extended period of time, but it believes that it might be able to release data from both of the soon-to-be initiated phase 3 studies using ORIC-944 and Enozertinib to treat patients with mCRPC and lung cancer, respectively. There actually is another move that helped it to be able to fund its company for this long period of time, and this was a $125 million private placement to raise cash to fund its operations. Along with the company noting that it had tapped into the at-the-market facility, raising approximately $119 million in cash during this most recent quarter.
Besides the thought of it being able to conserve cash going forward, what makes sense about the pipeline change is that it is set to potentially have to phase 3 studies underway in 2026. One program involves the use of ORIC-944 as a PRC2 inhibitor to treat patients with mCRPC. As the name suggests, prostate cancer is the growth of malignant cells on the prostate. However, this specific patient population has two other things to consider. The first of which is the term “metastatic,” which refers to the fact that the cancer itself has spread to other parts of the body. Then the castration-resistant portion denotes that the cancer continues to grow despite the patient being given androgen deprivation therapy (ADT).
PRC2 (Polycomb Repressive Complex 2) is a protein that is responsible for silencing gene expression. When this process is interrupted through either an increase or decrease of PRC2 activity in place, it leads to cancer development. Thus the use of ORIC-944 is to inhibit the dysregulation of PRC2 activity and prevent the growth of cancer. Furthermore, there are two druggable subunits of PRC2, which are EED and EZH2. The company believes that the route of targeting subunit EED is better because of possible resistance observed with subunit EZH2. Thus far the company is doing well in regard to this program, because it was able to release positive data from a phase 1b study.
This particular early-stage study evaluated the use of ORIC-944 in combination with androgen receptor (AR) inhibitors. With a cutoff date of May 9, 2025, it was revealed that about 59% of patients achieved PSA50. What this means is that this group of patients achieved a 50% or greater reduction in prostate-specific antigen (PSA) levels. This is important, because PSA is a measure put in place to determine disease activity. In essence, prostate cancer cells are being reduced by therapy. There are other efficacy endpoints in place that are further needed beyond the PSA50 response, but this preliminary data provides initial proof-of-concept that the company’s drug ORIC-944 indeed interrupts PRC2 activity.
Besides a phase 3 study program expected to be underway using this PRC2 inhibitor to target mCRPC patients at some point in 2026, there are other milestones to look forward to. One of which would be the release of additional ORIC-944 combination data (with AR inhibitors) in targeting these mCRPC patients in the 2nd half of 2025. Along with the goal of releasing dose optimization data from the very same program in Q1 of 2026. To that end, the company is also in the process of developing Enozertinib as a monotherapy, which is being developed to target advanced non-small cell lung cancer (NSCLC) patients with typical and atypical mutations (less common mutation types of lung cancer).
Furthermore, going after both 1st-line and 2nd-line mutation types. This brain-penetrant inhibitor targets the following lung cancer types: EGFR exon 20, HER2 exon 20, and EGFR atypical mutations (again, uncommon mutation cancer types). The use of this drug to target these NSCLC patients is being explored in an ongoing phase 1b study. Not only that, but there is the expectation that there will be data releases from this early-stage trial in the 2nd half of 2025 and mid-2026.