Cogent Biosciences: APEX Data Was Interesting, But We Need More (NASDAQ:COGT)

Cogent Biosciences (NASDAQ:COGT) was formerly known as Unum Therapeutics, a deadbeat company which, with its last breath, acquired an asset from a small company, did a reverse split of its shares, and ultimately renamed itself as Cogent. They say they are now “focused on developing precision therapies for genetically defined diseases.” Their lead program is bezuclastinib, “a selective tyrosine kinase inhibitor designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17.”

In a phase 1/2 trial, in over 50 patients with advanced solid tumors including gastrointestinal stromal tumors (“GIST”), the company says that anti-tumor activity was observed in both single agent and combination settings, including in combination with sunitinib, an approved treatment option for GIST patients. A confirmed objective response rate (“ORR”) of twenty percent was seen in these patients, including two partial responses and one complete response. Estimated median progression free survival (“mPFS”) was twelve months.

The company is now running a phase 3 trial called PEAK in GIST with bezuclastinib plus sunitinib versus sunitinib alone. This is a large, 426 patient study which will be toplined in July 2025. This is the company’s lead program.

Other programs include two phase 2 trials for the same molecule in varieties of mastocytosis. Just this month, the company published positive interim data from the APEX phase 2 trial in Systemic Mastocytosis. Data showed that all 11 patients achieved ≥50% reduction in serum tryptase levels, which is an important biomarker for mast cell activity. A number of other datapoints showed positive results. The molecule was generally well-tolerated, with no unexpected adverse events.

There are a number of tyrosine kinase inhibitors targeting KIT, such as imatinib, sunitinib, sorafenib, regorafenib, dasatinib, nilotinib, ponatinib, and midostaurin. Some of these are approved for GIST as well as for mastocytosis. I am not sure how bezuclastinib is differentiated from these others. Yes, the company does make a number of differentiations – bezuclastinib penetrates the brain less, it has potent activity against KIT Activation Loop Mutants, it has superior selectivity among closely related kinases, unlike other KIT inhibitors, and so on. However, all these need to be demonstrated in human trials, and until that happens, it is hard to differentiate bezuclastinib from all these well-established players.

Here’s a brief overview of the competition scenario from the company’s own 10-K:

In SM, the only approved drugs for the treatment of AdvSM are Blueprint Medicines Corporation’s avapritinib, Novartis AG’s midostaurin. Additionally, Novartis AG’s imatinib is approved for AdvSM patients without the KIT D816V mutation or mutational status unknown. We may face competition from other drug candidates in pre-clinical or clinical development for SM, including drug candidates from AB Sciences S.A, Allakos Inc., Celldex Therapeutics, Inc and Blueprint Medicines Corporation.

In GIST, the current approved standards of care for unresectable or metastatic patients are first-line imatinib, followed by second-line sunitinib upon imatinib progression, followed by third-line regorafenib upon sunitinib progression, followed by fourth-line ripretinib for patients who have received 3 or more prior kinase inhibitors. In addition, avapritinib was approved by the FDA in January 2020 for patients with GIST harboring a PDGFRα exon 18 mutation, including PDGFRA D842V mutations only. We may face competition from other drug candidates in pre-clinical or clinical development including, Arog Pharmaceuticals, Inc., Celldex Therapeutics, Inc., Taiho Pharmaceutical Co. Ltd, Xencor, Inc., and Theseus Pharmaceuticals, Inc.

Financials

COGT has a market cap of $854mn and a cash reserve of $191mn. Research and development expenses were $25.5 million for the first quarter of 2022 while general and administrative expenses were $5.9 million. That gives them a long cash runway, however with increasing later stage trials, expenses are sure to go up.

In May, the company announced a $300mn shelf offering, out of which, in June, it did an upsized $150mn stock offering.

The company derives its intellectual property through the acquisition of Kiq Bio LLC on July 6, 2020, through which they obtained an exclusive, sublicensable, worldwide license to patents and applications owned by Plexxikon pursuant to a license agreement between Plexxikon and Kiq.

Bottom line

Cogent looks interesting but not immediately investible because, in this bear market, investors need more derisked stocks. The APEX interim data has convinced us to keep watching this name; however, we will want to see more data from the various trials of bezuclastinib before we can make a decision to buy the stock.

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