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Overview

Tags

Neoplasms

Endocrinology and Metabolic Disease

Urogenital Diseases

Small molecule drug

Monoclonal antibody

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	3
Endocrinology and Metabolic Disease	1

Top 5 Drug Type	Count

Unknown	1
Small molecule drug	1
Monoclonal antibody	1

Top 5 Target	Count

CD44(CD44 antigen)	2

Author: de Meritens, Alexandre Buckley ; Wright, Jason D ; Hou, June ; Palmer, Joycelynne ; Rodriguez-Rodriguez, Lorna ; Girda, Eugenia ; Song, Mihae ; Yu, Hua ; Chan, Nancy ; Kohut, Adrian ; Martincuks, Antons ; Stephenson, Ruth ; Finlayson, Malcolm ; Tergas, Ana I ; Chekmareiva, Marina ; Nelson, David ; Vattakalam, Reena ; Leiser, Aliza

ObjectivePreclinical evidence and early clinical trials have demonstrated the activity of SPL-108, a targeted agent that inhibits CD44 mediated induction of multidrug resistance specifically to paclitaxel and platinum agents. We conducted a phase I, open label, dose escalation study of the safety and tolerability of the combination of SPL-108 with weekly paclitaxel in patients with platinum resistant CD44+ ovarian, primary peritoneal, or fallopian tube cancer.MethodsPatients with platinum resistant histologically proven epithelial ovarian, primary peritoneal, or fallopian tube cancers and measurable disease according to RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 were selected. Tumors were tested for CD44 expression for eligibility, defined as strong (+++) or moderate (++) staining in ≥20% of the tumor tissue or diffuse + staining. Patients were treated with daily and then twice daily SPL-108 subcutaneous injections and weekly intravenous paclitaxel on days 1, 8, and 15 of a 28 day cycle. Endpoints included safety, determination of maximum tolerated dose, and efficacy. Tumors underwent comprehensive genomic profiling, and cell lines and western blotting were used to study markers of response.ResultsWe screened 16 patients, and 14 were enrolled based on CD44+ expression. A total of 86% of patients had high grade serous tumors and all had received multiple prior therapies. There were no grade 4–5 toxicities. One patient had grade 3 peripheral sensory neuropathy attributed to paclitaxel and one patient developed presumed colonic perforation attributed to the study drug. No dose reductions or treatment discontinuations were required. All patients tolerated the maximum planned dose; no maximum tolerated dose was reached. Overall response rate was 36%; 5 (36%) patients had partial response and 5 (36%) patients had stable disease.ConclusionsThe combination of SPL-108 with weekly paclitaxel was safe and well tolerated. Encouraging antitumor activity was observed, with 72% of patients deriving a clinical benefit.Trial registrationNCT03078400.

20 May 2020·Journal of Clinical Oncology

Open label phase I trial using SPL-108 in combination with weekly paclitaxel final report with molecular correlates.

Author: Leiser, Aliza L. ; Stephenson, Ruth ; Finlayson, Malcolm ; Rodriguez-Rodriguez, Lorna ; Song, Mihae ; Buckley De Meritens, Alexandre ; Hou, June YiJuan ; Nelson, David M ; Girda, Eugenia

e18040 Background: Therapeutic options for patients with recurrent platinum resistant ovarian cancer are scarce and represent an unmet need in ovarian cancer. Chemotherapy resistance has been linked to many CD44 pathways including P-glycoprotein mediated efflux of chemotherapeutic agents. Our working hypothesis was that chemotherapy resistant ovarian tumors that expressed CD44 would revert drug resistance by using a CD44 inhibitor SPL-108, that had proven safe as a single agent. Methods: Patients with platinum refractory or resistant CD44+ ovarian tumors were eligible. We used a standard 3+3 phase I design, open-label, 2-arm trial of the combination of SPL-108 and IV paclitaxel (PTX): Arm 1 (2 cohorts) Safety Phase: Cohort 1: SPL-108 150 mg SQ Daily +80 mg PTX weekly Cohort 2: SPL-108 300mg daily +80 mg PTX weekly Arm 2 (1 cohort) Exploratory Phase: Cohort 3: SPL-108 daily dose 300 mg +80 mg PTX weekly Days 1-15 in 28 day cycles Primary end points were safety and tolerability. Secondary endpoints included determining molecular signatures of response using NGS. Tumors were sequenced at the time of recurrence or initial diagnosis. Results: Fourteen patients were enrolled in the study. Prior number of treatments ranged from 2-6, except for one patient with platinum refractory disease that progressed during first line of therapy. There was no DLT and all cohorts were completed as designed. The treatment was well tolerated. There was one instance of a bowel micro-perforation that was treated medically. This patient had platinum refractory disease and eventually underwent an interval cytoreduction. There was one patient with grade 3 neurotoxicity. Sixty-two% of the patients had clinical benefit with 36% having a PR. Forty-three % of patient had a PFS of more than 6 months. Two patients enjoyed a PR of 12 months. Molecular profiling of the tumors revealed that all tumors had TP53 alterations and the 4 patients that did not have a response had tumors with TP53 truncations or a lack of function alteration. Conclusions: Daily SPL-108 300mg SQ in combination with weekly PTX is safe and feasible. The promising clinical activity on drug resistant ovarian tumors warrants further investigation. Resistance to SPL-108 are characterized by lack of function of TP53, mostly early truncations. It is possible that SPL-108 may be reactivating TP53 by promoting its active conformation. Once TP53 is active CD44 expression is abrogated at the promoter. Therefore SPL-108 is effectively acting on CD44 through 2 different mechanisms to promote chemotherapy sensitivity. Clinical trial information: NCT03078400.

20 May 2018·Journal of Clinical Oncology

An open-label phase 1 trial of the safety and efficacy of daily subcutaneous SPL-108 injections when used in combination with paclitaxel in patients with platinum-resistant, CD44+, advanced ovarian epithelial cancer.

Author: Stephenson, Ruth ; Leiser, Aliza ; Finlayson, Malcolm ; Rodriguez-Rodriguez, Lorna ; Buckley de Meritens, Alexandre ; Girda, Eugenia ; Nelson, David ; Silverman, Michael H.

TPS5608Background: Ovarian cancer often presents in advanced stages and is treated with platinum-based chemotherapy. However, many patients develop platinum-resistant disease with either failing to...

100 Deals associated with Splash Pharmaceuticals, Inc.

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100 Translational Medicine associated with Splash Pharmaceuticals, Inc.

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Pipeline

Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Discovery

1

Preclinical

Phase 2 Clinical

1

2

Other

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

SPL-108 ( CD44 )	Ovarian Cancer More	Phase 2
SPL-110	Neoplasms More	Preclinical
US20230272103 ( CD44 )	Neoplasms More	Discovery
Angstrom-17	Neoplasms More	Pending
A-5 (Splash Pharmaceuticals) ( uPA )	Brain Cancer More	Pending