Aptose CEO Rice (R) with CEO Joo Jung-myeong of Crystal Genomics, Seoul, 2018. A milestone payment ceremony at CG, from which Aptose licensed malignancy-associated pan-tyrosine kinase inhibitor CG’806 for global development ex-Korea.

As we noted in our recent JPM coverage, Aptose plans to submit to the FDA an investigational new drug application (IND) later this month for CG’806. Rice and senior vice president and chief financial officer Gregory Chow appeared in fine form and upbeat recently  in San Francisco at bioweek. Ever the perfectionist, ever attuned to detail, Rice had recently completed personally drafting the CMC portion of the application. Without voicing any particulars, Chow expressed optimism that 2019 would see meaningful gains in both institutional involvement in Aptose share ownership and analyst coverage of the company; we noted that analysts ostensibly new to the Aptose situation seemed to be positively chomping at the bit to comment and express interest at the company’s recent KOL event, featuring Gleevec developer and Aptose SAB chairman Brian Druker, MD, director of OHSU’s Knight Cancer Institute in Portland, Oregon.

The Trump-driven government shutdown has raised some concerns among BioPub readers about timeline delays, and we reached out to Rice this morning about that situation. “Regarding the FDA,” he said, “the entire biotech industry is watching their actions. We too are hopeful that the government shutdown will not impact the CG’806 review process,” but he was quick to add he can give little formal guidance right now. The FDA is said to be operating with about 40 percent of its staff showing up for work, and to be honoring “grandfathered” commitments to review matters pertaining to drugs in development. Whether circumstances will delay FDA completion of the CG’806 IND review just can’t be known at present.

First–in-class and “founder” agent ibrutinib (Imbruvica) faced negative news this morning: Johnson and Johnson ($JNJ) and AbbVIe ($ABBV) have announced today that  the drug will fail to attain a seventh formal indication in pancreatic ductal adenocarcinoma. Recent trials were disappointing. Famously difficult to treat, pancreas cancer may harbor tyrosine kinase malignancy drivers that resist ibrutinib, and many such tyrosine kinases exist; likewise, as a covalent inhibitor, ibrutinib may cultivate resistant tumor, often rather rapidly.

CG’806 from Aptose is a non-covalent inhibitor efficacious at surprisingly low drug concentrations against Bruton’s tyrosine kinase (BTK, also covered by ibrutinib) and FLT3, a tyrosine kinase found in perhaps a third of AML patients and one prone to be present in mutant and resistant forms. Rice’s initial interest in CG’806 was wooed by how the drug is active against such divergent tyrosine kinases; BTK and FLT3 structurally have little in common, but both succumb readily to CG’806; Rice’s intuition has led to the discovery that CG’806 has activity against the entire kinome of malignancy-associated tyrosine kinases, including a plethora of resistant and mutant forms of these enzymes found uniquely in individual patients. While roughly half of patients dosed with ibrutinib have to discontinue that drug within 6 months of initiating therapy with it because of toxicity (toxicities were manifest in pre-clinical animal studies of ibrutinib but also deemed par for the course with a cancer drug), CG’806 thus far has evinced no genomic, metabolic, organ or hematologic toxicity in laboratory animals, even at stratospheric doses.

Regarding the Imbruvica and pancreatic cancer announcement, Rice said, “It’s no surprise, as pancreatic cancer is the graveyard for so many agents and patients.” AbbVie decided to pursue this potential indication only relatively late in ibrutinib’s development cycle, and likewise, pursuing CG’806 use in vexing solid tumors such as pancreatic cancer is not in Aptose’s near-term plans. The company seeks shots on goal as early as this year in AML and B-cell malignancies, where vast early promise is apparent from patient-derived xenograft models. Rice regards success in this arena as the most expeditious path for rewarding shareholders. Down the line, given world and time enough, he concedes that “it may be that CG-806 hits a sufficient number of pathways to truly affect pancreatic cancer,” but doesn’t want to jeopardize the business model by turning to such scenarios now, fraught as they are with risks of failure, including risks of failure unrelated to drug efficacy.

In San Francisco, Rice and Chow were clearly animated, even giddy, that CG’806’s advent into the clinic now draws so near.

“2019 is going to one incredibly interesting year for Aptose,” Rice said.

Disclosures: Of equities mentioned the author has a long position in $APTO and will not trade in $APTO shares for 7 business days following publication of this column. This article is not a recommendation for investment in Aptose shares and does not solicit the reader to so invest. The article is intended to facilitate but not replace due diligence by each would-be investor in $APTO stock. Copyright 2019 BioPub and the author; may not be reproduced without permission. BioPub and its editorial board have no business relationship with either Aptose Biosciences or its officers.