Spexis announces positive renal impairment clinical trial results with balixafortide

• Phase 1 clinical trial in patients with renal impairment demonstrates balixafortide to be safe and well tolerated
• Safety findings support potential to use significantly higher doses of balixafortide than those previously investigated
• Additional observations indicate potential for stimulating prolonged stem cell mobilization, a potentially key advantage in implementing hematopoietic stem cell transplantation

ALLSCHWIL, Switzerland, Sept. 22, 2022 (GLOBE NEWSWIRE) — Spexis AG (SIX: SPEX), a clinical-stage biopharmaceutical company focused on rare diseases and oncology, today announced the results of a Phase 1 clinical trial with balixafortide (“BLX”), a potent, specific and highly selective macrocycle inhibitor of CXCR4. This study was undertaken to investigate whether dosing of BLX needs to be adjusted in patients with renal impairment as part of any future market approval submission.

The Phase 1 trial was designed to investigate the pharmacokinetics, safety and tolerability of BLX in subjects with mild (n=8), moderate (n=8), or severe (n=7) renal impairment compared to a control group (n=8) with normal renal function. Each person received a single 2-hour intravenous infusion at the previously studied clinical dose of 5.5 mg/kg BLX.

In this trial, BLX was shown to be safe and well tolerated in all subjects, with only transient and mild-to-moderate manageable hypersensitivity-like events known to occur during initial drug infusion with CXCR4 inhibitors that were independent of renal impairment grade. With increasing grades of renal impairment, BLX administration resulted in more and longer-persisting circulating white blood cell levels, including neutrophils. Previous clinical trials with BLX at lower doses had demonstrated the ability to stimulate stem cell mobilization in healthy volunteers and in patients with advanced hematologic malignancies. The data from this renal impairment trial indicate that BLX doses substantially higher than 5.5 mg/kg, the highest dose previously tested, can potentially be safely administered, stimulate higher levels of stem cell mobilization and for longer durations well beyond 24 hours.

“The safety and pharmacokinetic findings in the renal impairment trial with balixafortide and data from previous nonclinical toxicity studies support potential dose levels of up to 16.5 mg/kg, which is threefold higher than previously studied dose levels. In addition, we are encouraged by the increases we observed in white blood cells and neutrophils, which support further clinical testing of balixafortide at higher dosing levels to assess its full potential in generating stem cell mobilization. Based on the results observed to date, we believe balixafortide may have the potential to generate more powerful stem cell mobilization than previously observed with CXCR4 inhibitors,” said Juergen Froehlich, MD, Chief Medical Officer of Spexis. “Patients with hematologic malignancies worldwide need additional highly effective treatment options in preparing for hematopoietic stem cell transplantation after treatment with high-dose chemotherapy. We look forward to further investigating the role balixafortide could play in this important area of cancer treatment.”

Increase of functional stem cells, also called mobilization, is an important prerequisite to the collection and transplantation of bone marrow cells in patients with hematologic malignancies. CXCR4 inhibition has been shown to be a viable approach to increase the yield of collecting stem cells from peripheral blood.¹ Hematologic malignancies occur due to uncontrolled growth of blood cells and lymphoid tissues and account for 6.5 % of cancers worldwide and approximately 9 % in Europe and the United States.²

References

¹https://stemcellres.biomedcentral.com/articles/10.1186/s13287-022-02802-6#Sec1
²https://ascopubs.org/doi/pdf/10.1200/JGO.19.00025

About Balixafortide (“BLX”)
Discovered from Spexis’ macrocycle platform, BLX is a potent, specific and highly selective macrocycle inhibitor of CXCR4 that plays a role in a number of tumor types as well as non-oncology indications. BLX has been studied in 8 clinical trials to date involving over 500 subjects and in multiple therapeutic indications such as solid tumors, hematologic malignancy and stem cell mobilization. Spexis has partnered China rights of BLX to Fosun Pharma, a leading Chinese pharmaceutical company. In addition, Spexis is analyzing existing BLX clinical and preclinical data to determine the appropriate development path forward, including potential new indications. In line with this ongoing review, Spexis recently published data demonstrating synergistic efficacy in combination with docetaxel in metastatic prostate cancer. These data, combined with the renal impairment clinical trial data announced today and other ongoing studies and analyses, will inform decisions on potential future development of BLX and related macrocycles within the Spexis portfolio.

About Spexis’ Macrocycle Platform:
Macrocycles are a proven chemical class of pharmaceutical therapeutics occupying the chemical space between small molecules and biologics. With a unique conformational balance of flexibility and rigidity, macrocycles can act on both extracellular and intracellular targets that are not easily accessible by other chemical classes. Indeed, since 2014, some 19 distinct macrocycle compounds have been approved by various drug regulatory authorities worldwide, involving a wide range of diseases and indications. More recently, with the emergence of the field of molecular glues and protein-protein interactions/degraders, macrocycles are increasingly recognized as possessing significant potential to target unique molecular targets and be combined with a variety of complementary technologies. Spexis possesses two distinct, highly diverse and well-characterized macrocycle libraries, together with deep data on same: PEMfinder^®, comprised of peptidomimetic macrocycles, and MacroFinder^®, comprised of small molecule macrocycles. Each library has distinct applications depending on the targets in question. In addition, Spexis has several pre-clinical leads for various indications which have already been considerably characterized. Spexis is looking to partner either these pre-clinical leads or the entire platform itself, potentially in combination with complementary technologies.

About Spexis
Spexis (SIX: SPEX) is a clinical-stage biopharmaceutical company based in Allschwil, Switzerland, focused on rare diseases and oncology. For further information please visit: www.spexisbio.com.

Disclaimer
This press release contains forward-looking statements which are based on current assumptions and forecasts of Spexis management. Known and unknown risks, uncertainties, and other factors could lead to material differences between the forward-looking statements made here and the actual development, in particular Spexis’ results, financial situation, and performance. Readers are cautioned not to put undue reliance on forward-looking statements, which speak only of the date of this communication. Spexis disclaims any intention or obligation to update and revise any forward-looking statements, whether as a result of new information, future events or otherwise.