On May 23, 2019 NewLink Genetics Corporation (NASDAQ:NLNK) reported the abstract (Poster 61) entitled, "A Phase 1 Clinical Trial of NLG802, a Prodrug of Indoximod with Enhanced Pharmacokinetic Properties," was presented at the Immuno-Oncology 2019 2nd World Congress in Barcelona, Spain (Press release, NewLink Genetics, MAY 23, 2019, View Source [SID1234536550]).

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The Phase 1 dose-escalation study evaluated the safety, toxicity and PK of NLG802 to determine the maximum tolerated dose (MTD) or maximum biologically achievable dose (MBAD). Data from the study was used to recommend a Phase 2 dose (RP2D) of NLG802.

NLG802 was administered orally at five dose levels up to 1452 mg BID in 26 patients with recurrent advanced solid tumors. At the time of analysis for this presentation, five (19%) patients remain on study, 14 (54%) alive, and four patients withdrew from follow-up. Six patients achieved a best response of stable disease per RECIST 1.1 criteria, with 1 patient having durable stable disease greater than nine months. No subject experienced a dose-limiting toxicity within the first 28-day cycle. The most frequently reported adverse events (AE) regardless of attribution were fatigue (54%), nausea (46%), vomiting (35%), decreased appetite (31%), and diarrhea (23%).

PK results were also reported from this study. After continuous twice-daily dosing with NLG802 at all levels, significantly higher PK exposure was observed. At 1452 mg BID, the highest dose administered, NLG802 produced a 6-fold increase in Cmax and a 4.7-fold increase in AUC compared with molar equivalent indoximod dosing.

The treatment regimen was well tolerated with no NLG802-related serious adverse events (SAE) reported. MTD/MBAD had not been reached, and recommended Phase 2 dose (RP2D) was established at 1452 mg BID based on achieving preclinical exposure levels required for pharmacodynamic effects of indoximod.

An interesting response was observed during this study involving a patient with metastatic pancreatic cancer who had failed three prior lines of therapy (gemcitabine plus nab-paclitaxel, FOLFIRI, and irinotecan HCl plus gemcitabine). NLG802 was administered to this patient as 4th line therapy and was discontinued after five weeks upon disease progression. The patient was subsequently re-challenged with gemcitabine plus nab-paclitaxel. Imaging three months after re-challenge showed a partial response (PR) with 75% reduction in total tumor burden. In addition, the CA19-9 levels dropped 94% from levels prior to this line of therapy. No objective responses were observed after any earlier rounds of chemotherapy prior to administration of NLG802. This suggests that prior treatment with NLG802 may have contributed to the response ultimately observed in this patient.

"These results corroborate earlier data demonstrating NLG802’s ability to produce significantly higher exposure levels in patients compared with molar equivalent dosing of indoximod, while maintaining tolerability," said Eugene P. Kennedy, MD, Chief Medical Officer of NewLink Genetics. "We are encouraged by these results, which reinforce our belief that NLG802 has the potential to be an important component of an immuno-oncology treatment regimen."

The poster can be accessed through the NewLink Genetics website at www.NewLinkGenetics.com in the "Investors & Media" section under "Posters & Presentations" or by clicking here.

About NLG802

NLG802, an orally-available prodrug of indoximod, was specifically engineered to increase the bioavailability of indoximod by leveraging existing mechanisms of absorption, increasing the exposure of indoximod approximately 5-fold. NewLink Genetics is currently evaluating NLG802 in a Phase 1 dose-escalation clinical trial in cancer patients to assess the safety and pharmacokinetics of NLG802.