TNGX - Tango Therapeutics: Partial Phase 1 Data Has Not Helped

2023-07-26 19:29:51 ET

Summary

• In my previous article, I hoped that Tango publishing POC data would help the stock.
• They published partial data, and it was not convincing.
• The stock remains stagnant.

I was hoping for some spike on early data update from TNG908, a small molecule developed by Tango Therapeutics ( TNGX ) as a synthetic lethal inhibitor of PRMT5 or protein arginine methyltransferase 5. However, the event went by, but the stock stayed stagnant. There has been a steady fall in value since mid-January, and the data update did not help in the stock’s recovery.

Tango is a developer of synthetic lethality. Synthetic lethality occurs between two genes when both of them are artificially perturbed in such a manner that both of them lose viability, which they would not have lost if they had been perturbed individually. Tango uses synthetic lethality to address tumor suppressor gene loss in specific patient populations. Lead asset TNG908 is a small molecule synthetic lethal inhibitor of PRMT5 or protein arginine methyltransferase 5 and MTAP, the relevant synthetic lethal pair.

TNG908 exclusively targets cancer cells with MTAP deletion. Preclinical data shows a 15-fold greater potency versus normal cells. MTAP deletion occurs in 10-15% of all human tumors, including 40% of glioblastomas; 25% of melanomas, urothelial carcinomas, and pancreatic adenocarcinomas; and 15% of non-small cell lung carcinomas (NSCLC). They began a phase 1 trial in patients last year, whose data update they had planned for mid-2023. The importance of this catalyst was that it was the first proof of concept of this interesting science.

The company hasn’t actually presented a press release for this data. The trial pipeline is here, from tickerbay.com :

If you click on the NCT ID, you should be able to see data if it has been “properly” release, but there’s nothing relevant:

But if you check the two updates they provided during the March and May earnings, and compare them for material on TNG908, you get this:

March PR

TNG908, an MTA-cooperative PRMT5 inhibitor

• Patients are actively being enrolled in the Phase 1/2 clinical trial. Based on a recent protocol amendment, glioblastoma ((GBM)) patients will be added to the ongoing trial.

May PR

TNG908 proof-of-mechanism demonstrated with marked differential PRMT5 inhibition in MTAP-deleted cancers versus normal tissue

• As of May 9, 16 patients with MTAP-deleted solid tumors representing 12 different histologies across four cohorts have been treated, and dose escalation is continuing.

• Favorable pharmacokinetics with dose-proportional increases in exposure across cohorts.

• TNG908 proof-of-mechanism as an MTA-cooperative PRMT5 inhibitor demonstrated by marked SDMA reduction in MTAP-deleted cancer cells versus normal tissue. SDMA is a direct measure of TNG908 target engagement and PRMT5 inhibition.

• Pre-treatment and on-treatment biopsies (cycle 2/day 1) demonstrated dose-dependent decreases in tumor SDMA with minimal or no decrease in normal tissue. Selective inhibition of PRMT5 in MTAP-deleted cancer cells is essential to enable the therapeutic index needed for efficacy.

• TNG908 exposure in cohorts 1 and 2, while sufficient to show marked differential effects on SDMA, is not yet within the efficacious range predicted by preclinical modeling.

• Dose levels 3 and 4 ongoing, cohorts not yet evaluable for efficacy.

• To-date, no dose-limiting toxicities (DLTs) or greater than grade 2 related adverse events have been observed. Notably, there has been no evidence of bone marrow suppression as determined by peripheral blood counts.

So this is the data, however, there does not appear to be a specific press release for the release of this data, not even on the company website:

How many times have you seen an emerging biopharma not announcing as loudly as possible even tentative early signs of any positive data, especially when they are the first proof of concept data?

If you look at the data, though, TNG908 showed high levels of specificity, and bone marrow suppression has also not been observed. So the molecule appears safe. But note that sentence - “TNG908 exposure in cohorts 1 and 2, while sufficient to show marked differential effects on SDMA, is not yet within the efficacious range predicted by preclinical modeling.” The two other cohorts were also not yet evaluable for efficacy. I think this here is the problem part - that either it is too early for efficacy data, or there is none. I think this is why the company did not do a press release, and this is also why the stock has stayed subdued. “Not yet” is not yet bad, but it is an anticlimax and not good either.

TNG908 is brain penetrating, and glioblastoma has 40% of patients with MTAP deletion, so glioblastoma is a natural target for TNG908. Recently, the company presented data at AACR2023 which showed that TNG908 is efficacious in preclinical models. Two other trials, for TNG260 Phase 1/2 Trial in patients With STK11-Mutant cancers, and for TNG462 Phase 1/2 Trial in Patients With MTAP-deleted Solid Tumors, first patients have been dosed. TNG462 is a superior version of TNG908.

Financials

TNGX has a market cap of $279mn and a cash balance of $336mn, which includes $6mn in collab revenue. Research and development expenses were $28.0 million for the three months ended March 31, 2023, while general and administrative expenses were $8.0 million. That gives them a long, 9-quarter cash runway. While having more cash than they are valued at is good if you want to park your money somewhere safely, it also shows the market’s utter lack of respect for the pipeline.

TNGX is principally owned by institutions followed by PE/VC firms, with a small 5% stake owned by the retail public. This sort of ownership structure indicates legacy enthusiasm, but lack of retail interest shows the broad market disinterest. Key holders are Third Rock Ventures, BCTG Holdings etc. There are few insider purchases, and no sells.

Bottom Line

In my last article, I said I liked TNGX, and the POC data may pop the stock. Either they did not produce complete data, or the data wasn’t good enough, yet. Look at it either way, TNGX remains stagnant. I think I will keep watching this for now.

For further details see: