"All there is to investing is picking good stocks at good times and staying with them as long as they remain good companies", said Warren Buffet, reminding us that patience and discipline are key to successful investing. Stocks quietly climbing to new 52-week highs could be a sign that the market is recognizing consistent performance, strong fundamentals, or upcoming catalysts.The following are some of the stocks that hit new 52-week highs yesterday. Do you already own any of them? Are any on your watchlis ...

Bezuclastinib Program - Bezuclastinib is a potential best-in-class selective KIT mutant inhibitor, showing promise in pre-clinical studies and Phase 1/2 trials for GIST patients[10, 115] - KIT mutations drive up to 80% of GIST and over 90% of SM cases[27] - Bezuclastinib exhibits minimal brain penetration, with a brain to plasma ratio of 007, compared to 20 for avapritinib[37] - Cogent is conducting a Phase 2 clinical study (APEX) of Bezuclastinib in patients with Advanced Systemic Mastocytosis, with initial clinical results expected in 1H 2022[47, 48] FGFR2 Program - FGFR2 and FGFR3 are collectively altered in up to 41% of cancers[55] - Cogent is developing FGFR2 selective inhibitors with a target profile of <10 nM FGFR2 Cell IC50 and >200 nM FGFR1 Cell IC50[64] - CGT0292, a lead compound, demonstrates ~30x selectivity between FGFR1 and FGFR2 in cellular assays[80] - CGT0292 does not show serum phosphorus increase at a 5 mg/kg dose in the SD Rat Model of Hyperphosphatemia[84] ErbB2 Program - Significant unmet need remains for patients with non-exon 20 ErbB2 mutations[95] - Cogent is developing an ErbB2 mutant selective drug which covers key mutations while sparing wtEGFR, with a target Mutant Cell IC 50 of <10 nM and EGFR WT Cell IC 50 of >200 nM[104, 105] - Cogent has identified several novel series with promising enzyme selectivity for ErbB2 over EGFR WT[114] Financial Status - Cogent Biosciences had a cash balance of $2197 million as of December 31, 2021[12, 117]

Bezuclastinib Clinical Programs - Bezuclastinib combined with sunitinib demonstrated a 12-month median Progression-Free Survival (mPFS) in heavily pre-treated Gastrointestinal Stromal Tumors (GIST) patients[10] - In the APEX study, initial data in Advanced Systemic Mastocytosis (AdvSM) patients shows promising clinical activity with Bezuclastinib[10] - In Apex study, the Overall Response Rate (ORR) of CR + CRh + PR + CI was 73% (8 out of 11 patients) per CRRC assessment in TKI therapy-naïve AdvSM patients[27] - In Apex study, 88% of patients achieved a ≥ 50% reduction in serum tryptase levels[35] - In Apex study, 100% of patients with at least 2 cycles of treatment achieved a ≥ 50% reduction in bone marrow mast cell burden[35] - In Apex study, 92% of patients with at least 2 cycles of treatment achieved a ≥ 50% reduction in KIT D816V VAF[35] Market Opportunity - The global Total Addressable Market (TAM) potential for Bezuclastinib exceeds $3.5 billion, including $1.5 billion for NonAdvSM, $700 million for 2nd-line GIST, and $300 million for AdvSM[14] - Approximately 90% of Systemic Mastocytosis (SM) patients present with non-advanced systemic mastocytosis (NonAdvSM)[18] - Approximately 10% of patients present with advanced systemic mastocytosis (AdvSM)[18] Pipeline and Financials - The company's research pipeline includes novel, small-molecule targeted therapies for rare diseases, including an FGFR1-sparing, pan-mutant FGFR2 and a CNS-penetrant ErbB2[7] - The company's cash runway is expected to fund operations into 2025, with $289.1 million in cash as of September 30, 2022[7, 83]

Clinical Programs & Catalysts - Cogent Biosciences has multiple clinical and preclinical programs with upcoming catalysts, including top-line results for Bezuclastinib in AdvSM expected in July 2025, NonAdvSM in 2H 2025, and GIST by EOY 2025 [7, 8, 11] - The company is conducting a registration-directed study of Bezuclastinib in NonAdvSM with 179 patients, using a 24-week MS2D2 primary endpoint [11] - A registration-directed study of Bezuclastinib monotherapy is underway in AdvSM with 58 patients, using ORR as the primary endpoint [11] - PEAK Part 2 is a global Phase 3 trial of Bezuclastinib in 2nd-line GIST, with top-line results expected by the end of 2025 [8] Financial Position - As of Q1 2025, Cogent Biosciences has $245.7 million, expected to fund operations into late 2026 [9] Market Opportunity - The aggregate US annual sales opportunity for Bezuclastinib across AdvSM, NonAdvSM, and GIST is greater than $3 billion with limited competition [12] - The US annual market opportunity for NonAdvSM is estimated at $2 billion, with differentiated symptom improvement potentially leading to market leadership [11] - The US annual market opportunity for 2nd-line GIST is estimated at over $1 billion, with limited competition [11] - The US annual market opportunity for AdvSM is estimated at $300 million, with differentiated safety/tolerability results potentially leading to market leadership [11] Competitive Landscape - Cogent believes Bezuclastinib offers a best-in-class KIT inhibitor opportunity with minimal late-stage competitive activity [10, 13, 30] Safety and Efficacy - In ISM patients, only 25% of Ayvakit patients achieved clinically meaningful improvement [18] - In PIONEER Part 2, low-dose Ayvakit (25 mg once daily) was associated with an improved safety profile, with 13% experiencing eye edema and dizziness [19]