5 Philly Life Sciences Companies We're Watching in H1 2023

In a year full of challenges, the Philadelphia life sciences ecosystem continued its string of successes. Despite the consistent volatility, last year certainly meant financial success for many local companies. In fact, pharmaceutical giant Merck, headquartered in nearby Rahway, New Jersey, posted its best year in almost a decade.  

Last year also brought considerable enthusiasm in other areas as well. There were plenty of R&D successes to be found, including movement of Annovis Bio’s oral treatment for Parkinson’s disease into Phase 3 clinical trials.

The financial and research successes contributed to a strong life sciences jobs outlook. In response to the growing need for workers, local industry has partnered with governmental and advocacy groups in new training efforts to support the local workforce.

Even as 2023 brings continued economic uncertainty, the Philly life sciences community has much to be optimistic about. Here are five companies whose potential 2023 achievements make them worthy of attention in the first half of the year.

iECURE

iECURE was founded to pursue gene therapy giant James Wilson’s goal of curing genetic diseases by integrating healthy genes into patients’ chromosomes.

A key innovation in the strategy employed by iECURE is the use of the ARCUS gene editing method pioneered by Precision BioSciences. This method makes use of a cell-deliverable nuclease to digest the genome in a defined region, allowing for the highly specific insertion of a healthy gene.

Scientists at iECURE have focused their efforts on Wilson’s original target: ornithine decarboxylase deficiency, an inborn disease of the urea cycle. During the second half of 2022, the company was awarded both rare pediatric disease and orphan disease designations for a drug developed at the GTP, GTP-506. This treatment involves the delivery of two viral vectors. One virus directs the expression of the ARCUS nuclease. The nuclease facilitates stable genomic insertion of the second bit of cargo, a healthy copy of the gene encoding ornithine decarboxylase.

GTP-506 showed promise in preclinical mouse and non-human primate studies, giving the company optimism as it moves forward with its treatment of OTC. More importantly, the stable insertion of the gene in these models helps to validate the overall process. The company has multiple diseases in its sights, with treatments for citrullinemia type 1 and phenylketonuria in the discovery phase.

The demonstrated potential of iECURE’s strategy has translated into funding. The company began in September of 2021 with $50 million of Series A financing, and an additional $65 million was procured in November of 2022 during a Series A-1 round.

Capstan Therapeutics

Most cell therapies involve the manipulation of cells ex vivo: outside of the patient. Based on technology developed by CAR T pioneer Carl June and other UPenn-based experts, Capstan has pioneered a precision delivery system that permits them to explore the engineering of cells in vivo. Their innovative virus-free delivery system uses targeted lipid nanoparticles (tLNP) to deliver cargo to specific cells. Unlike viruses, which are limited to ferrying nucleic acids, these nanoparticles can deliver a variety of molecules, including DNA and gene editing machinery but also translatable mRNA or ready-made therapeutic proteins.

Their strategy promises to provide flexibility to the application of CAR T therapy to cancer and to facilitate the development of cell therapies for other diseases, especially those characterized by fibrotic tissue that can be trimmed away by properly instructed immune cells.

The potential utility of tLNPs has been supported by recently published pre-clinical data. A team of researchers used this delivery strategy to modify T cells in situ to produce a chimeric antigen receptor targeting fibrotic tissue in a mouse model of heart disease. These CAR T-cells, which were generated within the bodies of the mice, destroyed fibrotic tissue and restored cardiac function.

This early success garnered the attention of the VC arms of several big pharma companies and facilitated the launch of Capstan in September of 2022. Capstan will be entering 2023 with exciting results and $165 million from a consortium of VC investors.  

Galera Therapeutics

While oxygen supports life, its characteristic reactivity can lead to decay. Cells have some capacity to protect biochemical structures from reactive oxygen-containing compounds, but under aberrant conditions, this capacity can be overwhelmed.

One mechanism by which radiation therapy kills cancer cells is by the localized generation of superoxide and other reactive oxygen species. Unfortunately, superoxide can also damage nearby healthy tissue ⎼ severe oral mucositis (SOM) is a common manifestation of this damage, especially in patients undergoing treatment for head and neck cancers.

SOM can have a devastating effect on cancer patients, and there are no currently approved treatments.

Galera’s key agents support cells’ superoxide-scavenging capabilities. Their small-molecule compounds are mimetics of the cellular dismutase enzymes that can’t keep up with the rapid generation of superoxide stimulated by radiation. The manganese-based therapeutic agents decompose superoxide into peroxides that maintain their destructive potential against cancer cells but are readily neutralized by healthy cells.

Their lead drug candidate, avasopasem manganese, led to significant improvement of SOM in certain patients in two late-phase clinical trials published in 2022, and a new drug application has been submitted to the FDA. This drug is also moving forward through clinical trials for another application: radiotherapy-induced esophagitis that accompanies radiation treatment for lung cancer.

A second drug candidate, rucosopasem manganese, is in clinical development as an agent to enhance the effectiveness of radiotherapy treatment in the context of multiple cancers.

With several radical new treatment strategies and a pending new drug application, expect Galera to make some bold moves early in 2023.

Venatorx Pharmaceuticals

While it does not tend to get the same press as viral pathogens, the growing menace of bacterial antibiotic resistance is an equally dire, but perhaps less well publicized, threat to humanity.

Enter Venatorx. The company is on the hunt for new anti-infective agents to combat challenging bacterial pathogens that are resistant to the current front-line antibiotics. The work of Venatorx has garnered the attention of the FDA in the form of multiple Fast Track designations. It has also struck the interest of a biomedical research funding arm of the federal government, who has funded the work to the tune of more than $300 million.

Venatorx has multiple financing streams, including the initiation of sales of Series C Preferred Stock during the first half of 2022.

The company has reported positive results from Phase 3 trials of its lead formulation, cefepime-taniborbactam. This antibacterial agent consists of a broad-spectrum, beta-lactam antibiotic (cefepime), in combination with an inhibitor (taniborbactam) of bacterial enzymes that frequently inactivate beta-lactams. A Phase 1 trial of an oral formulation is underway, and other clinical trials are focusing on safety and efficacy in juvenile patients.

Venatorx expects to submit a new drug application on behalf of cefepime-taniborbactam during the first half of 2023.

A second antibacterial formulation combines the cyclosporin-class antibiotic ceftibuten with the beta-lactamase inhibitor ledaborbactam. This combination has shown activity against several multi-drug resistant bacteria, and Phase 1 clinical studies have been completed.

With multiple promising strategies for combating bacterial drug resistance and a healthy influx of funding, Venatorx has momentum that could translate to a newsworthy 2023.

SparingVision

Philly’s Spark has been the focal point of treatments for inherited retinal diseases since its revolutionary gene therapy agent was approved by the FDA in 2017. Spark’s treatment, Luxurna (voretigene neparvovec) has certainly achieved success in preventing blindness. However, since it is designed to deliver a healthy copy of a damaged gene, it is only useful for a limited number of patients who have mutations in that particular gene (RPE65).

SparingVision, a French company with US headquarters in Philadelphia, has a somewhat wider view of RP, as its lead agent (SPVN06) is designed to provide efficacy independent of the underlying genetic cause of the disorder. SPVN06 involves viral-mediated delivery of two genes directly into the retinal light-sensitive cells that are lost in RP-mediated blindness. While many in vivo gene therapy strategies, such as those of iECURE, seek to replace defective genes with active, healthy copies, SparingVision’s strategy is to provide cells with two proteins that support the survival of weakened photoreceptor cells. This support occurs essentially independently of the genetic defect that leads to the weakness.

One of the genes that the virus inserts into patients’ genomes encodes a growth factor. This protein works to slow or even stop the degeneration of the retinal neuronal cells. The second gene delivers a protein with potent antioxidant activity. Similar in principle to Galera’s small-molecule dismutase mimetics, this second protein protects the target cells against the ravages of aberrantly produced reactive oxygen species.

While SPVN06 is not quite ready for widespread clinical application, SparingVision’s future is bright, as plans are underway for Phase 1/2 studies – the company expects that 2023 will bring safety data that may pave the way for additional human studies.

These trials, and those of a second vision-targeted gene therapy asset, will be supported with €75 Million of Series B funding procured during the second half of 2022.