Benzinga | May 26, 2021 07:41AM EDT

Progenity Provides Results From Key Study For Its Targeted Therapeutics Program

Progenity, Inc. (NASDAQ:PROG), an innovative biotechnology company, today announced results from a further study for the company's Targeted Therapeutics program. The study evaluated delivery of Progenity's PGN-001 (adalimumab) drug substance directly to the colon in a preclinical model of colitis.

Progenity's Targeted Therapeutics program consists of drug-device combination products under development that have the potential to deliver high concentrations of proprietary drug formulations via a novel, orally ingestible capsule to the precise site of disease along the gastrointestinal (GI) tract. The Drug Delivery System (DDS) capsule is designed to maximize the available dose at the site of disease to potentially improve efficacy and reduce systemic toxicity.

Progenity's lead Targeted Therapeutics product candidates, PGN-001 (liquid adalimumab delivered by DDS) and PGN-600 (liquid tofacitinib delivered by DDS), are being developed with an initial priority for ulcerative colitis, part of the estimated $15 billion inflammatory bowel disease market.

The company completed a preclinical study evaluating the tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of adalimumab liquid formulation (PGN-001 drug substance) delivered directly to the colon through local administration to the cecum in a swine model of induced colitis. PGN-001 drug substance was delivered in either single administration or daily repeat administration for three days by a surgically implanted intracecal (IC) catheter as a surrogate for direct delivery to the colon by the DDS. The study included healthy and induced colitis vehicle control groups.

The study found that adalimumab was detected in tissue along the length of the colon after IC administration. There was also a significant reduction in TNF-?, the proinflammatory cytokine target of adalimumab, at each of 24 and 48 hours following repeat IC doses when compared with the induced colitis control group that did not receive treatment. No treatment-related adverse events were observed and no measurable adalimumab was detected in the blood, in each case, for animals administered adalimumab by IC catheter.

"These results suggest targeted topical delivery of adalimumab may provide an advantage over systemic delivery by substantially reducing the TNF-? burden within the colonic tissue with little to no systemic breakthrough. These results are made even more impressive as adalimumab has significantly lower affinity for pig TNF-? compared to human. Not only does this support the potential use of PGN-001 as monotherapy but also as combination therapy given the minimal systemic levels and associated safety margin," said William Sandborn, MD, Professor of Medicine at the University of California San Diego.

This study builds upon data Progenity previously presented at Digestive Disease Week 2019 from a mouse model of colitis that used a species-appropriate TNF-? monoclonal antibody delivered by IC catheter. The 2019 study found that targeted IC delivery significantly reduced weight loss, decreased Disease Activity Index, improved histological score and reduced tissue inflammatory cytokines in mice when compared with vehicle controls. The 2021 study in swine models more closely represents human anatomy, allows for use of PGN-001 drug substance, and therefore provides more robust data for the potential effect in humans.

"These preclinical results provide further evidence that therapies delivered locally in the GI tract have the potential to transform the treatment of ulcerative colitis by maximizing the available dose at the site of disease while reducing systemic exposure to improve safety. We now have evidence that this is not just the case for small molecules but also for monoclonal antibodies. This opens the potential for additional candidates for our Targeted Therapeutics program, as well as pharmaceutical and biotech partnerships," said Harry Stylli, PhD, CEO, chairman of the board and co-founder of Progenity.

The company is currently performing a clinical study to obtain further supporting data for the local delivery of adalimumab, using administration by enema as a surrogate for delivery with the DDS. Preliminary results are expected this year and should further guide dosing as Progenity advances towards clinical evaluation of adalimumab delivered by the DDS in ulcerative colitis patients.

The Targeted Therapeutics program is further supported by additional data previously announced by Progenity:

* Preclinical data presented at DDW 2021 demonstrating the functionality of the Drug Delivery System capsule, in which the DDS capsule successfully identified the colonic entry and delivered drugs to the colon after oral administration in fasted animal models.

* Preclinical data presented at DDW 2021 indicating that targeted delivery of proprietary, soluble tofacitinib (PGN-600) to the site of inflammation has the potential to increase tissue absorption and coverage and reduce systemic toxicity.

* Preclinical results showing that the DDS in combination with proprietary, soluble tofacitinib (PGN-600) achieved a greater than 25-fold increase in drug delivery to colon tissue vs. equivalent orally administered dose. PGN-600 also demonstrated reduced systemic breakthrough.

* Clinical study results demonstrating that the DDS was able to target the colon and successfully release a liquid payload with pan-colonic distribution as observed by imaging, in normal healthy volunteers.

Progenity also recently announced funding from the Crohn's and Colitis Foundation to support the development and further clinical evaluation of the DDS.