G1 Therapeutics (NASDAQ:GTHX) is up 50% since my April write-up. The upward movement started from mid-June, and when I am looking for reasons, I see this – the last patient has been randomized in the Phase 3 clinical trial of trilaciclib for patients with metastatic colorectal cancer (mCRC) receiving chemotherapy (PRESERVE 1). That means, the trial is now fully enrolled.
In order to understand why this is important, go through my earlier articles quickly. While trilaciclib is already FDA approved to mitigate chemotherapy-induced myelosuppression in adult patients with small cell lung cancer, the stock has been struggling to make money, and mCRC and TNBC are its big indications. The stock was down for a long time after trilaciclib’s approval because the drug wasn’t making enough money for the company. The principal reason for this was GTHX was not able to find the right marketing partner for its drug, and was thus unable to access the big accounts despite getting reimbursement with a permanent J-code. However, SCLC is a much smaller market than either mCRC or TNBC, and being tumor-agnostic, trilaciclib is eventually going to get approved in these indications. The PRESERVE-1 trial will topline in November this year, while TNBC will be 2-3 years later. The excitement surrounding GTHX is because of mCRC data readout.
Here’s what PRESERVE-1 looks like:
PRESERVE 1 is a global multi-center, randomized placebo-controlled, line extension pivotal Phase 3 trial of trilaciclib in 326 patients with metastatic CRC receiving first line trilaciclib or placebo administered prior to FOLFOXIRI (a combination of fluorouracil (5-FU), folinic acid, oxaliplatin and irinotecan) and bevacizumab. The regimen is given for two consecutive days of every 14-day cycle. Patients are receiving trilaciclib or placebo administered prior to their chemotherapy for a maximum of 12 cycles of induction followed by maintenance therapy. Treatment is administered until disease progression.
There are 150,000 US patients with Colorectal cancer, most of whom receive 5-FU based chemotherapy regimen. CRC is the second most common cause of cancer death, representing about 12-14% of all cases. Around 25% of patients present with metastasis at diagnosis, which can eventually go up to 50%. Looking at the numbers, mCRC is about thrice the target market compared to SCLC, which is one reason for recent excitement surrounding trilaciclib. The entire CRC market is estimated to be around $20bn, while SCLC is about a third of that.
Most mCRC patients receive a combination of leucovorin, fluorouracil, oxaliplatin, and irinotecan in the first-line setting, often in combination with a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) pathways. While treatment quality has vastly improved over the years, it has also led to increased toxicity, specifically from induced myelosuppression and its resultant problems. This has caused the chemo regimen to be used mainly in younger patients with fewer comorbidities. Trilaciclib is intended to reduce myelosuppression in a lineage-agnostic manner, meaning it is useful whether you have developed neutropenia, anemia or thrombocytopenia.
There are no specific phase 2 trials in mCRC available. However:
• Data from 3 randomized, placebo-controlled, phase 2 clinical trials showed that administering trilaciclib prior to chemotherapy reduced the incidence of chemotherapy-induced myelosuppression, and reduced the need for supportive care interventions and chemotherapy dose reductions/delays
• Additionally, in a randomized phase 2 trial in patients with metastatic triple-negative breast cancer, administering trilaciclib prior to gemcitabine plus carboplatin significantly improved OS compared with chemotherapy alone, potentially through protection and direct activation of immune function
The PRESERVE-1 study is overenrolled to compensate for loss of patient data in Ukraine due to the ongoing war. November topline data will act as a major catalyst for the stock. From all indications and past data in other cancer types, trilaciclib will have absolutely no trouble in succeeding in this trial.
GTHX has a market cap of $356mn and a cash balance of $183mn. The company made $6.9mn in COSELA sales in the last quarter. Operating expenses for the first quarter of 2022 were $53.7 million, which included R&D and G&A expenses of $26.3 million and $26.7 million respectively. This gives them a cash runway of around 3 quarters.
GTHX is looking attractive once again. The stock is up 50% since my last coverage, although it is still not near the levels it was earlier in 2021. I am strongly considering re-entering the stock to take advantage of the November data readout and eventual label expansion.
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