SR419 / Shanghai SIMR Biotech - LARVOL DELTA

Quantitative Sensory Testing of SR419, a First-in-Class Oral α5-GABAA Receptor Negative Allosteric Modulator, in Neuropathic Pain Patients (PAINWeek 2025) - P1, P1/2 | "Participants had a mean age of 66.8 ± 9.31 years (range: 50-81 years), w ith 80% being male . Following administration of a single dose of SR419 (20 mg), pregabalin (150 mg or 300 mg), or placebo to patients with DPN (n = 10), PHN (n = 6), or idiopathic neuropathy (n=8), no significant differences were observed in QST components (DMA, MDT, MPT, WDT, CDT, HPT, CPT) or the overall QST score (△QST) at the affected area across treatment groups, based on parameters including absolute value, E max , and AUC. SR419 and pregabalin exhibited similar effect profiles on QST parameters, although pregabalin demonstrated greater efficacy than SR419 at the affected site."

Clinical • Addiction (Opioid and Alcohol) • CNS Disorders • Musculoskeletal Pain • Neuralgia • Pain • Peripheral Neuropathic Pain

Synthesis and evaluation of a novel inhibitor for the α5-GABAA receptor in the treatment of peripheral neuralgia: Evidence from MD simulation and in vivo studies. (PubMed, Br J Pharmacol) - "SR-419 is a peripherally acting GABRA5 inhibitor with potent analgesic efficacy and a favourable safety profile. Its target-specific mechanism suggests that it is a promising candidate for treating PNP and avoiding central side effects."

Journal • Preclinical • Anesthesia • Neuralgia • Pain • Peripheral Neuropathic Pain

A Phase 1b Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SR419 (clinicaltrials.gov) - P1/2 | N=24 | Completed | Sponsor: Shanghai SIMR Biotechnology Co., Ltd. | Phase classification: P1b ➔ P1/2

Phase classification • Neuralgia • Pain • Peripheral Neuropathic Pain

To Evaluate the Efficacy and Safety of SR419 in Patients With Postherpetic Neuralgia (PHN) (clinicaltrials.gov) - P2 | N=83 | Completed | Sponsor: Shanghai SIMR Biotechnology Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Neuralgia • Pain

To Evaluate the Efficacy and Safety of SR419 in Patients With Postherpetic Neuralgia (PHN) (clinicaltrials.gov) - P2 | N=83 | Active, not recruiting | Sponsor: Shanghai SIMR Biotechnology Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2023 ➔ Jan 2023

Enrollment closed • Trial completion date • Neuralgia • Pain

Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer Cells: Implications for Targeted Therapy. (PubMed, Mol Cancer Ther) - "Here, we show that a combination of insulin and the GPCR agonist neurotensin induced rapid activation of Src family of tyrosine kinases (SFKs) within PANC-1 cells, as shown by FAK phosphorylation at Tyr576/577 and Tyr861, sensitive biomarkers of SFK activity within intact cells and Src419 autophosphorylation. Crucially, SFKs promoted YAP nuclear localization and phosphorylation at Tyr357, as shown by using the SFK inhibitors dasatinib, saracatinib, the preferential YES1 inhibitor CH6953755, short interfering RNA (siRNA)-mediated knockdown of YES1 and transfection of epitogue-tagged YAP mutants in PANC-1 and MiaPaCa-2 cancer cells, models of the aggressive squamous subtype of PDAC...A combination of dasatinib and trametinib potently and synergistically inhibited colony formation by PDAC cells and suppessed the growth of MiaPaCa-2 cells xenografted into the flank of nude mice. The results provide rationale for considering a combination(s) of FDA-approved SFK (dasatinib)..."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • IGF1

A Phase 1b Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SR419 (clinicaltrials.gov) - P1b | N=24 | Completed | Sponsor: SIMR (Australia) Biotech Pty Ltd. | Recruiting ➔ Completed | Trial completion date: Dec 2021 ➔ Jul 2022 | Trial primary completion date: Dec 2021 ➔ May 2022

Trial completion • Trial completion date • Trial primary completion date • Neuralgia • Pain • Peripheral Neuropathic Pain

The Pharmacokinetics (PK), Safety, Tolerability of SR419 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Shanghai SIMRD Biotechnology Co., Ltd. | Trial completion date: Dec 2021 ➔ May 2022

Trial completion date

To Evaluate the Efficacy and Safety of SR419 in Patients With Postherpetic Neuralgia (PHN) (clinicaltrials.gov) - P2 | N=82 | Recruiting | Sponsor: Shanghai SIMR Biotechnology Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Neuralgia • Pain

To Evaluate the Efficacy and Safety of SR419 in Patients With Postherpetic Neuralgia (PHN) (clinicaltrials.gov) - P2 | N=82 | Not yet recruiting | Sponsor: Shanghai SIMR Biotechnology Co., Ltd.

New P2 trial • Neuralgia • Pain

The Pharmacokinetics (PK), Safety, Tolerability of SR419 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Shanghai SIMRD Biotechnology Co., Ltd. | Recruiting ➔ Completed

Trial completion

The Pharmacokinetics (PK), Safety, Tolerability of SR419 in Healthy Volunteers (clinicaltrials.gov) - P1; N=32; Recruiting; Sponsor: Shanghai SIMRD Biotechnology Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

The Pharmacokinetics (PK), Safety, Tolerability of SR419 in Healthy Volunteers (clinicaltrials.gov) - P1; N=32; Not yet recruiting; Sponsor: Shanghai SIMRD Biotechnology Co., Ltd.

Clinical • New P1 trial

A Phase 1b Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SR419 (clinicaltrials.gov) - P1b; N=24; Recruiting; Sponsor: SIMR (Australia) Biotech Pty Ltd.; Trial completion date: Jun 2021 ➔ Dec 2021; Trial primary completion date: Jun 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Neuralgia • Pain • Peripheral Neuropathic Pain

A Study to Assess the Pharmacokinetics and Food Effect of SR419 in Healthy Subjects (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: SIMR (Australia) Biotech Pty Ltd; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Pharmacokinetics and Food Effect of SR419 in Healthy Subjects (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: SIMR (Australia) Biotech Pty Ltd; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study to Assess the Pharmacokinetics and Food Effect of SR419 in Healthy Subjects (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: SIMR (Australia) Biotech Pty Ltd

Clinical • New P1 trial

A Phase 1b Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SR419 (clinicaltrials.gov) - P1b; N=24; Recruiting; Sponsor: SIMR (Australia) Biotech Pty Ltd; Trial completion date: Jan 2021 ➔ Jun 2021; Trial primary completion date: Jan 2021 ➔ Jun 2021

Clinical • Trial completion date • Trial primary completion date • Neuralgia • Pain • Peripheral Neuropathic Pain

A Phase 1b Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SR419 (clinicaltrials.gov) - P1b; N=24; Recruiting; Sponsor: SIMR (Australia) Biotech Pty Ltd; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Key Milestone: The first patient successfully dosed with the candidate drug SR419 for peripheral neuropathic pain (PRNewswire) - "Shanghai SIMR Biotechnology Co., Ltd....announced that, the clinical trial in patients with peripheral neuropathic pain has been initiated for the candidate drug SR419, and the first patient has been successfully dosed. The current clinical trial is the first study for SR419 in the patient population, purposing to explore the efficacy, safety, tolerability and pharmacokinetics of SR419 in patients with neuropathic pain."

New trial • Trial status • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

A Phase 1b Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SR419 (clinicaltrials.gov) - P1b; N=24; Not yet recruiting; Sponsor: SIMR (Australia) Biotech Pty Ltd

Clinical • New P1 trial • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

The Safety, Tolerability, Pharmacokinetics(PK) of SR419 in Healthy Volunteers (clinicaltrials.gov) - P1; N=64; Completed; Sponsor: SIMR (Australia) Biotech Pty Ltd; Recruiting ➔ Completed

Clinical • Trial completion

Chinese chronic pain reliever begins clinical trial (xinhuanet) - "A new Chinese drug to alleviate patients' neuropathic pain, or nerve pain, has entered clinical trials, according to the Ministry of Science and Technology Tuesday....Data shows that the incidence of neuropathic pain among Chinese elderly is 49.8 percent and more than 50 percent in cancer patients. Conventional painkillers are largely ineffective."

New trial