- Pivotal study to assess whether treatment with Ladarixin, which inhibits the biological activity of IL-8, is effective in delaying the progression of T1D in adolescents and newly-diagnosed adults

- First patient treated at Università Campus Bio-Medico di Roma, Rome, Italy; U.S. sites to follow in first half of 2021

Dompé farmaceutici s.p.a and Dompé U.S. Inc., (collectively Dompé) announced today that the first patient has been enrolled in its Phase 3 trial evaluating the efficacy and safety of Ladarixin in adolescents and adults with new-onset type 1 diabetes (T1D).

The Phase 3 trial of Ladarixin, a novel, oral, small molecule drug, will be conducted as a randomized, multicenter, double-blind, placebo-controlled study. The primary endpoint is to assess effectiveness in preserving β-cell function by inhibiting the biological activity of IL-8. Recruitment for U.S. trial sites is underway, with studies planned to begin in the first half of 2021. European trial site recruitment will continue until 2022.

“We are excited to take the next step in recognizing the potential of IL-8 inhibition for new-onset type-1 diabetes patients through treatment with Ladarixin. After years of collaboration with diabetes experts from around the world, we hope that this trial will offer critical evidence that interrupting the inflammatory cascade in type-1 diabetes is possible.” said Marcello Allegretti, PhD Chief Scientific Officer of Dompé.

The Phase 3 trial of Ladarixin follow Phase 2 trial results, which were presented at the 2020 virtual American Diabetes Association’s Scientific Sessions and published in the June 2020 edition of Diabetes.

In the Phase 2 study, no clinically relevant safety observations were detected between the two groups studied.1 Furthermore, in the Phase 2 study, new approaches for inhibition of IL-8, a pro-inflammatory mediator involved in the innate immune response, more recently known as CXCL-8, showed promising effects on the preservation of pancreatic β-cells and slowing the progression of disease in patients with new-onset T1D.2 Overall, Ladarixin was well-tolerated.

About Type 1 Diabetes (T1D)

T1D is a chronic autoimmune disease that, over time, results in an immune-mediated loss of functional pancreatic β-cell mass, leading to symptomatic diabetes and lifelong insulin dependence.[1],[2] Currently available treatment approaches focus on glycemic control and do not address the high unmet medical need of delaying disease progression by preserving β-cell function.[3]

CXCL-8, a pro-inflammatory chemokine also known as IL-8, is an important mediator in several immune and metabolic disorders, including T1D.[4] Modulation or inhibition of CXCL-8 activity through blockade of its cellular receptors, CXCR1/2, may be considered a target for the development of innovative treatments aimed at slowing the progression of T1D.[5]

About Ladarixin

Ladarixin is an investigational, oral, small-molecule that functions as a non-competitive, dual allosteric inhibitor of CXCL8 (IL-8) receptors, CXCR1 and CXCR2. By blocking CXCR1/2 receptors, Ladarixin may prevent inflammation- and immune system-mediated destruction of β-cells in pancreatic islets that is a hallmark of T1D.2 CXCR1/2 inhibition has been shown to prevent and to reverse T1D in mice.[6] Ladarixin is not approved for use in any country.

About GLADIATOR, the Phase 3 Study of Oral Ladarixin in New-onset Type 1 Diabetes and a Low Residual β-cell Function (ClinicalTrials.gov Identifier: NCT04628481).

GLADIATOR is a Phase 3, multicenter, double-blind, placebo-controlled study designed to further evaluate the efficacy and safety of Ladarixin in preserving β-cell function and slowing progression of type 1 diabetes (T1D) in adolescent and adult subjects with new-onset T1D and low residual β-cell function at baseline.

The study will be conducted in about 40 study centers in the European Union, United States and other countries, if appropriated. The study will enroll approximately 327 patients across all study centers with new-onset T1D, including approximately 200 adolescents (ages 14-17 years).

Following a run-in period and randomization visit, participating subjects will be randomly (2:1) assigned to receive either Ladarixin treatment (400 mg twice daily for 13 cycles of 14 days on/14 days off) or matching placebo. Subjects will receive Ladarixin or placebo for 12 months, and then followed for an additional 12 months from the start of treatment.

About Dompé

Dompé is a private, rapidly scaling global biopharmaceutical company founded in Milan, Italy, with a 130-year legacy of medical innovation. Today, Dompé employs more than 800 employees worldwide and maintains a U.S. commercial operations hub in the San Francisco Bay Area as well as an R&D presence in Boston.

Forward Looking Statements

This press release refers to certain information that may not coincide with expected future results. Dompé firmly believes in the soundness and reasonableness of the concepts expressed. However, some of the information is subject to a certain degree of indetermination in relation to its research and development activities and the necessary verifications to be performed by regulatory bodies. Therefore, as of today, Dompé cannot guarantee that the expected results will be consistent with the information provided above.

References

[1] Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. The Lancet 2014, 383:69-82.

[2] Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med1986;314:1360–1368.

[3] Mittermayer F, Caveney E, De Oliveira C, Fleming GA, Gourgiotis L, Puri M, Tai LJ, Turner JR. Addressing Unmet Medical Needs in Type 1 Diabetes: A Review of Drugs Under Development. Curr Diabetes Rev. 2017;13(3):300-314.

[4] Alnek K, Kisand K, Heilman K, Peet A, Varik K, Uibo R (2015) Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes. PLoS ONE 10(12): e0142976.

[5] Linhartova PB, Kavrikova D, Tomandlova M et al. Differences in Interleukin-8 Plasma Levels between Diabetic Patients and Healthy Individuals Independently on Their Periodontal Status. Intl J Molec Sci. 2018; 19 (3214): 1-17.

[6] Citro A, Valle A, Cantarelli E, et al. CXCR1/2 inhibition blocks and reverses type 1 diabetes in mice. Diabetes 2015; 64: 1329-40.