German and U.S. biotech venture InflaRX has been showcased before in one of our TrialSite News Hidradenitis Suppurativa (HS) articles. They recently announced promising news about their IFX-1 lead candidate for HS. What follows is a summary of the InflaRX and their HS lead drug candidate INFX-1.
Who is InflaRx N.V.?
InflaRX N.V. (IFRX) is a clinical-stage biopharmaceutical company focused on applying its proprietary anti-C5a technology to discovery and develop first-in-class, potent and specific inhibitors of C5a. Complement C5a is a powerful inflammatory mediator in the progression of a wide variety of autoimmune and other inflammatory diseases. Their IFX-1 is a monoclonal antibody which specifically binds to the soluble human complement split product C5a. Nonclinical studies have demonstrated that IFX-1 binds to its target rapidly and is capable of a nearly complete blockade of C5a-induced biological effects while not affecting cleavage of C5 and formation of the complement membrane attack complex (MAC). Founded in 2007, the company maintains offices in Jena and Munich, Germany as well as Ann Arbor, MI and New York, NY. Company founders include Niels Riedemann and Renfeng Guo, a professor at University of Michigan. The two founders launched InflaRx to develop new therapeutics in the field of acute and chronic inflammation. After raising rounds of venture capital, the team announced an initial public offering (IPO) November 2017; they were able to execute a successful follow on offering as well.
The firm is in a race to secure approval of next generation treatments including for Hidradenitis Suppurativa. Time is of the essence. Drug development is a time-consuming and expensive process and investors only have so much patience. Despite being publicly traded, finances are tight. According to Yahoo Finance, they operated at a loss of over $20 million last year. A pre-revenue company, they currently maintain a market capitalization of $859 million.
They face prominent risk factors as articulated in their initial offering documentation. They include:
- History of significant operating losses—they expect to incur more losses and will need additional capital
- Clinical trials are expensive, time consuming and outcomes are uncertain
- Clinical failure can occur despite success during preclinical
- They are heavily dependent on lead candidate IFX-1—if it is not approved their entire company at risk
- Substantial competition from other HS biotechs such as XBiotech to HUMIRA
- Undesirable side effects may be generated during later clinical trials
- Opportunity costs associated with critical decisions as to investment choices
The stock has constraints as nearly 50% of the holders are insiders. Their 52-week high/low includes $20.31 to $42.83—current price is $33.50. Recently, JPMorgan Chase & Co boosted InflaRx target price to $65—a good sign for the commercial sponsor. They note that although some equities analysts, such as Zacks Investment Research downgraded InflaRx shares from a “buy” to a “hold” rating other such as ValuEngine raised from hold to buy. Last year, Seeking Alpha’s Jonathan Faison reported that InflaRx shares have risen by 60% by May of 2018. The equities analyst commented that there were a few positive signals for IFRX including:
- Hidradenitis Suppurativa looks to be a potentially lucrative market opportunity
- Prior data provides significant derisking and the recent secondary offering extends their operational runway (e.g. more capital to operate)
- IFX-1 appears to have “the makings of a pipeline in a product”
The company leverages their proprietary anti-C5a technology for two programs including IFX-1 and IFX-2. IFX-1 includes a phase II Hidradenitis Suppurative trial as well as trial focused on ANCA associated vasculitis (AAV) as well as other autoimmune disease work and preclinical oncology. As the company reports, IFX-1 is a first-in-class monoclonal anti-human complement factor C5a antibody, which effectively blocks the biological activity of C5a and demonstrates high selectivity towards its target in human blood. Thus, IFX-1 leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism, which is not the case for molecules blocking the cleavage of C5. IFX-1 has been demonstrated to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key “amplifier” of this response in pre-clinical studies. IFX-1 is believed to be the first monoclonal anti-C5a antibody introduced into clinical development and has, to date, successfully completed three clinical phase II studies. More than 150 people have been treated with IFX-1 in these completed clinical trials, and the antibody has been shown to be well tolerated. IFX-1 is currently being developed for various inflammatory indications, including Hidradenitis Suppurativa and ANCA-associated vasculitis. The IFX-2 program includes pre-clinical work associated with chronic inflammatory and autoimmune diseases.
Hidradenitis Suppurative Investigational Treatment
TrialSite News was requested by several viewers to summarize InflaRx’s Hidradenitis Suppurative investigational drug. Most recently, InflaRx announced new IFX-1 HS clinical data from one of its clinical trials. Presenting to the 8th Conference of the European Hidradenitis Suppurativa Foundation in Wroclaw, Poland, the company summarized positive findings for this painful and debilitating chronic inflammatory skin disease with limited treatment options. Sharing retrospective long-term data from their phase IIa trial, which focused on moderate to severe HS, the primary goal of the trial was to evaluate the safety and tolerability of IFX-1 administered over eight weeks in these patients. Additionally, the trial aimed to characterize the pharmacokinetics and pharmacodynamics of IFX-1 as well as to generate preliminary data on the efficacy of IFX-1 on clinical endpoints (e.g., Hidradenitis Suppurativa Clinical Response (HiSCR); Dermatology Life Quality Index (DLQI); Visual Analog Scale (VAS) for disease; VAS for pain; Hidradenitis Suppurativa—Physician’s Global Assessment (HS-PGA); Modified Sartorius Score (mSS)).
Phase IIa Hidradenitis Suppurative Study
The results of this trial, reported February 8th, are from an additional retrospective evaluation of the long-term effect of IFX-1 post treatment. TrialSite News provides a link to the company’s presentations here. Ten of the 12 patients were available for this analysis. The median observation period after the last IFX-1 treatment was 226 days (range 119 to 324 days). The long-term efficacy was assessed by the abscess and inflammatory nodule count (AN count), number of draining fistulas, HiSCR assessment, and the occurrence of flares. Flares were defined as deterioration of HS requiring antibiotic therapy.
As reported by the German sponsor, two flares occurred during the treatment period, and two flares occurred during the scheduled follow-up period. In the long-term follow-up, there were 26 flares, ranging from two to four per patient. The median time to the first flare after stopping IFX-1 treatment was 209 days (range 54 to 318 days), while off medication, 50% of patients had no flares to day 203.
Moreover, the sponsor reported that further analysis of AN county, number of draining fistulas, and HiSCR supported the assumption of the long-lasting effect of IFX-1 after treatment stopped.
This study was conducted at ATTIKON University Hospital in Athens, Greece. The principal investigator, Dr. med. Evangelos J. Giamarellos-Bourboulis noted, “It is gratifying to see that sustained remission was observed in most patients treated with IFX-1. It is notable that only 8 weeks of treatment, the median time to the first flare up was almost seven months. With limited options for Hidradenitis Suppurativa, there is a major need to find more effective therapies that can provide relief over an extended period. I look forward to seeing the results from the ongoing randomized study with IFX-1 in this indication, which should give us additional insight into the efficacy and safety of this novel treatment for this debilitating condition.”
Ongoing Phase IIb HS Study
Dr. Giamarellos-Bourboulis is also involved with the ongoing phase IIb study. With 175 participants, the study has been set up based on the hypothesis that IFX-1 might be able to block C5a induced pro-inflammatory effects such as neutrophil activation and cytokine generation, potentially contributing to the local skin inflammation and tissue damage. The objective of this trial is to evaluate a dose response signal of IFX-1 with HiSCR at week 16. They announced completion of enrollment in November 2018. A blinded snapshot of the clinical database was performed and available data from 179 patients at baseline are being reported.
- 56% of patients female
- 44% of patients male
- Mean age 37.1 years old
- Mean body weight 92.2 kg (203lbs)
- Median duration of HS was 8 years
- 59.1% and 41% of patients were classified as Hurley Stage 2 or 3 respectively
- Median inflammatory nodule count at baseline was 9 (range 3 to 58)
The sponsor reports that the described baseline demographical data and characteristics are in-line with the overall moderate to severe HS population. The topline results from the phase IIb study are expected during the quarter 2, 2019. InflaRx Chief Medical Officer, Othmar Zenker, MD, reports that the trial is advancing according to plan. Mr. Zenker noted, “The goal of with this trial is to determine the optimal dose regimen, as well as assess both the long-term efficacy and safety of IFX-1 in patients with the disease.”
InflaRX is in a race to secure approval of next generation treatments including for Hidradenitis Suppurative. Time is of the essence. Their IFX-1 is a monoclonal antibody which specifically binds to the soluble human complement split product C5a. Nonclinical studies have demonstrated that IFX-1 binds to its target rapidly and is capable of a nearly complete blockade of C5a-induced biological effects while not affecting cleavage of C5 and formation of the complement membrane attack complex (MAC). IFX-1 tested in phase IIa study for moderate to severe HS show promising results. Phase IIb study is ongoing and sponsor InflaRX is confident about outcomes. On one hand, prominent equity analysts believe the stock price should be higher. Others are more cautious. Obviously if this result is stellar, this introduces the possibility for a phase III and ultimately submission to Food and Drug Administration (FDA) and European Medicines Agency (EMA) for what we hope to be a superior treatment for Hidradenitis Suppurative. As with other sponsors in pursuit of HS treatments such as XBiotech, TrialSite News will be monitoring the situation carefully.
Mr. O’Connor has spent nearly 20 years providing technology and value-added services to the clinical trials and health technology industry. An entrepreneur, he has been instrumental in building different ventures focusing on FDA 21 Part 11 enterprise document management, technology-enabled patient recruitment services, clinical safety data exchange, as well as population health and community care coordination for at-risk populations with Eccovia Solutions. He is a co-founder of a public benefit corporation launching a global clinical research site accreditation standard–ACRES ReServ. At TrialSite News, Mr. O’Connor and team have developed a comprehensive clinical research site data base and intelligent clinical news curation engine to contribute to clinical research transparency with a focus on sites and investigators. He earned his combined MA and JD from the University of California (Los Angeles and Hastings College of the Law) and undergraduate from San Francisco State University.