SNDX - Syndax Pharmaceuticals: 2023 Is A Pivotal Year

Summary

• Syndax Pharmaceuticals, Inc. has two pivotal trials with data readouts coming up in 2023, with possible regulatory filings.
• They are loaded with cash after a successful offering.
• Despite current highs, I see further upside in 2023.

Syndax Pharmaceuticals, Inc. ( SNDX ) is a late-stage developer of cancer therapies. Its lead asset is a Menin inhibitor called revumenib, which is targeting various acute leukemias in three pivotal trials which are enrolling patients. Five years ago, when I first covered SNDX, they had a lead molecule called etinostat targeting breast cancers. SNDX stock is up 250% since then, however, etinostat is now almost out of the pipeline after multiple failures to demonstrate a survival benefit. However, the two other candidates, revumenib and axilitinib, also in a pivotal trial in GvHD, have fared better for the company.

Here’s the pipeline:

Lead asset revumenib is a menin inhibitor. Menin inhibitors are a new class of therapeutics being studied extensively for leukemias. Preclinical studies have shown that inhibition of the Menin-MLL1 interaction caused apoptosis. In 2020, phase 1 data was published. Data showed that “SNDX-5613 [revumenib] turns off leukemic transcriptional programs by binding to Menin and displacing MLL complexes.” There were two arms with different dose levels, and dose proportional exposure was achieved in both arms. There were no discontinuations due to treatment related adverse events. The company says the treatment was well-tolerated across all doses. However, there were a number of patients reporting grade 3 or above ECG QTc prolongation at various doses, which is always a cause for worry.

However, safety signals were good with 55% ORR and 24% CR. Broadly, the phase 1 trial was able to confirm the therapeutic value of the molecule’s mechanism of action.

Updated data from this same trial showed a slight improvement in ORR and CR and a percentage decline in QTc prolongation. 30% of patients attained CR/CRh with a median duration of 9.1 months. This data, published in December 2022, compares favorably with menin inhibitor rival Kura Oncology ( KURA ), who also published data at the same time. A pivotal portion of the AUGMENT101 study is enrolling relapsed/refractory (R/R) patients across distinct trial populations: patients with nucleophosmin mutant (mNPM1) acute myeloid leukemia ((AML)), patients with KMT2Ar AML, and patients with KMT2Ar acute lymphocytic leukemia ((ALL)). Each of these indications may lead to regulatory filings.

Covering Kura last month, I wrote the following about Syndax which covers the situation:

Thus the SNDX data appeared much better than Kura’s, and investors punished Kura with a 14% drop on that day, while SNDX gained 14%. Two years earlier, too, SNDX was the leader that was able to pull the menin inhibition space up. At that time, SNDX posted positive data that helped pull up KURA stock, not just SNDX. However, as the two assets are becoming increasingly differentiated, that sort of “sympathetic detonation” is not happening any longer. Syndax has its own problems with cardiac toxicity, but revumenib targets a broader population.

Second asset is axatilimab targeting GvHD and partnered with Incyte ( INCY ). About this molecule, the company states :

Donor-derived, pro-inflammatory macrophages are dependent on CSF-1R signaling and have been shown in preclinical studies to be responsible for symptoms associated with chronic graft versus host disease (cGVHD). Syndax believes that CSF-1R blockade with axatilimab (SNDX-6352) may reduce the number of these pro-inflammatory macrophages and play a meaningful role in the treatment of chronic graft versus host disease.

This asset is currently running the AGAVE trial, described thus:

A Pivotal Trial to Evaluate the Efficacy, Safety and Tolerability of Axatilimab at 3 Different Doses in Patients With Recurrent or Refractory Active Chronic Graft Versus Host Disease Who Have Received at Least 2 Lines of Systemic Therapy

This molecule has been trialed in multiple indications including solid tumors, covid-19 and now GvHD. A phase 1 trial has shown proof of concept in GvHD in the second line setting where few therapies exist; ibrutinib is currently used but has several limitations.

2023 is an important year for Syndax because it plans to publish data from two pivotal trials, AUGMENT101 beginning 3Q 2023 for leukemias, and AGAVE-201 in mid 2023 for GvHD. The company may be granted facility for rolling NDA and BLA submission, in which case expect multiple applications this year. Revumenib comes with a breakthrough therapy designation. As the company noted yesterday:

For revumenib, we are on track to begin reporting topline data from the AUGMENT-101 pivotal trial in the third quarter of this year, with the first data expected to be in patients with KMT2A rearranged (KMT2Ar) acute leukemia and expect to file a New Drug Application (NDA) by year-end 2023. For axatilimab, we also remain on track to report topline results from our pivotal AGAVE-201 trial in chronic graft versus host disease (cGVHD) in mid-2023, with a Biologics License Application ((BLA)) filing expected to follow by year-end 2023. We look forward to providing updates on all of our progress as we continue to strive toward our mission of realizing a future in which people with cancer live longer and better than ever before.

Financials

SNDX has a market cap of $1.73bn and a cash balance of $481mn after raising $150mn in December through a secondary offering. Fourth quarter 2022 research and development expenses were $31.8 million, while general and administrative expenses were $10.2 million. At that rate, the company is well-funded for 10 more quarters.

Bottomline

Syndax Pharmaceuticals, Inc. is well-funded and is a leader in its space. It has two upcoming pivotal data drops and then regulatory filings this year. While Syndax Pharmaceuticals, Inc. stock is trading near 52-week highs, the target markets are large enough to merit further upside for SNDX stock if the company is able to do well in its pivotal trials. As such, I might be a Syndax Pharmaceuticals, Inc. buyer even at these prices.

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