remetinostat (SHP-141) / Medivir, Biossil - LARVOL DELTA

Medivir grants global rights to Biossil for remetinostat (PharmaTimes) - "Under the terms of the deal, Biossil will receive worldwide rights to develop remetinostat, which has shown positive data in basal cell carcinoma and cutaneous T-cell lymphoma. If successfully developed and approved, Medivir could receive up to USD 60 million in milestone payments, along with mid-single digit royalties on future net sales."

Licensing / partnership • Basal Cell Carcinoma • Cutaneous T-cell Lymphoma

Topical histone Deacetylase Inhibitor Remetinostat improves IMQ-induced psoriatic dermatitis via suppressing dendritic cell maturation and keratinocyte differentiation and inflammation. (PubMed, Eur J Pharmacol) - "In this study, the topical application of remetinostat significantly improved psoriasiform inflammation in an imiquimod-induced mice model by inhibiting CD86 expression of CD11C+I-A/I-E+ dendritic cells (DCs) in the skin. In addition, remetinostat can promote keratinocyte differentiation without affecting its proliferation. Our findings demonstrate that remetinostat improves psoriasis by inhibiting the maturation and activation of DCs and the differentiation and inflammation of keratinocytes, which may facilitate the potential application of remetinostat in anti-psoriasis therapy."

Epigenetic controller • Journal • Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • CD86 • ITGAX

Soft drug inhibitors for the epigenetic targets lysine-specific demethylase 1 and histone deacetylases. (PubMed, Arch Pharm (Weinheim)) - "This has been successfully applied for corticosteroids in the clinic, but soft drugs targeting epigenetic enzymes are scarce, with the HDAC inhibitor remetinostat being the only example. We have developed new methyl ester-containing inhibitors targeting LSD1 or HDACs and compared the biological activities of these to their respective carboxylic acid cleavage products. In vitro activity assays, cellular experiments, and a stability assay identified potent HDAC and LSD1 soft drug candidates that are superior to their corresponding carboxylic acids in cellular models."

Epigenetic controller • Journal • CNS Disorders • Mental Retardation • Oncology • Psychiatry

Nitrilase mediated mild hydrolysis of a carbon-14 nitrile for the radiosynthesis of 4-(7-hydroxycarbamoyl-[1- C-heptanoyl]-oxy)-benzoic acid methyl ester, [ C]-SHP-141: a novel class I/II histone deacetylase (HDAC) inhibitor. (PubMed, J Labelled Comp Radiopharm) - "The final step involved deprotection of the benzyloxy group using catalytic hydrogenation to facilitate the release of the hydroxamic acid without cleaving the phenoxy ester. [ C]-SHP-141 was isolated with a radiochemical purity of 90% and a specific activity of 190 μCi/mg from four radiochemical steps starting from potassium [ C]-cyanide in a radiochemical yield of 45%."

Epigenetic controller • Journal

Recent advances in chemical composition and transdermal delivery systems for topical bio-actives in skin cancer. (PubMed, Curr Top Med Chem) - "The most commonly used topical agents for treating skin carcinoma are- 5-fluorouracil, imiquimod, sonidegib, dacarbazine, etc. However, drug physicochemical characteristics and skin physiological barriers limit the anticancer potency of topical as well as transdermal drug delivery. In particular, significant studies have been made, including modification of bio-actives, permeability enhancers, incorporation of advanced nano and microcarriers, and physical enhancement devices. This critical review summarizes the advancement in the chemical composition of bioactives used in skin cancer, such as sinecatechins, BIL-010t, patidegib, gingerol, curcumin, remetinostat, epigallocatechin-3-gallate, etc. Furthermore, this review, specifically addresses the progress in transdermal delivery systems for melanoma and non-melanoma cancer therapy, emphasizing advances in physical and chemical penetration enhancement and nanocarrier-assisted transdermal systems."

Journal • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma

Treatment of Cutaneous Squamous Cell Carcinoma With the Topical Histone Deacetylase Inhibitor Remetinostat. (PubMed, JAMA Dermatol) - No abstract available

Epigenetic controller • Journal • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Results from investigator-initiated phase II clinical study of remetinostat in patients with squamous cell carcinoma published (PRNewswire) - "Medivir AB...announces that results from the investigator-initiated phase II clinical study in patients with squamous cell carcinoma...Four patients with five biopsy-proven cutaneous SCCs were included in this case series and treated with remetinostat gel 1%. All five tumours, including a range of histological subtypes, demonstrated complete clinical and pathological resolution at week 10. All patients experienced a localized cutaneous reaction in response to the treatment, which required one patient to discontinue therapy. No systemic adverse events were reported."

P2 data • Oncology • Squamous Cell Carcinoma

"Medivir strengthens the business development potential of remetinostat through renegotiated multi-party agreement https://t.co/g6gWAfYkbG" (@CisionNews)

Positive data from the remetinostat phase II study in basal cell carcinoma published in Clinical Cancer Research (PRNewswire) - P2, N=30; NCT03180528; "Medivir AB...announced...that positive data from the investigator-initiated study evaluating the effects of remetinostat in basal cell carcinoma (BCC) patients has been published in Clinical Cancer Research....Thirty-three per-protocol tumors from 25 participants were included in the analysis. The overall response rate (ORR), defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8, was 69.7% [90% confidence interval (CI), 54%–82.5%]."

P2 data • Basal Cell Carcinoma • Oncology

Phase II Open-Label, Single-Arm Trial to Investigate the Efficacy and Safety of Topical Remetinostat Gel in Patients with Basal Cell Carcinoma. (PubMed, Clin Cancer Res) - "The HDAC inhibitor remetinostat is a well-tolerated and effective topical treatment for reducing BCC disease burden in a clinically significant manner. This provides in-human validation of HDAC inhibitors as a therapy for BCC."

Clinical • Journal • P2 data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Topical Remetinostat in Treating Patient With Cutaneous Basal Cell Cancer (clinicaltrials.gov) - P2; N=30; Completed; Sponsor: Kavita Sarin; Active, not recruiting ➔ Completed

Clinical • Trial completion • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • GLI1 • STAT3

Positive results from investigator-initiated phase II clinical study of remetinostat in patients with squamous cell carcinoma published (PRNewswire) - P2, N=4; NCT03875859; "All five tumours, including a range of histological subtypes, demonstrated complete clinical and pathological resolution after up to 8 weeks of treatment. All patients experienced a localized cutaneous reaction in response to the treatment, which required one patient to discontinue therapy. No systemic adverse events were reported."

P2 data • Oncology • Squamous Cell Carcinoma

[VIRTUAL] Is topical remetinostat gel an effective and safe treatment for basal cell carcinoma? Results of a phase 2, open label, single arm trial (SID 2021) - "Remetinostat, a topical pan-HDAC inhibitor, is a safe and effective topical treatment for BCC, reducing disease burden in a clinically significant manner. Our results provide the first in-human validation of HDAC inhibitors as a potential therapeutic."

Clinical • P2 data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Topical Remetinostat Gel as Neoadjuvant Therapy in Patients With Squamous Cell Carcinoma (SCC) (clinicaltrials.gov) - P2; N=4; Terminated; Sponsor: Kavita Sarin; N=40 ➔ 4; Trial completion date: Oct 2021 ➔ Jan 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Apr 2021 ➔ May 2020; The available study medication reached expiry (logistics).

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology • Squamous Cell Carcinoma • STAT3

Topical Remetinostat Gel as Neoadjuvant Therapy in Patients With Squamous Cell Carcinoma (SCC) (clinicaltrials.gov) - P2; N=40; Active, not recruiting; Sponsor: Kavita Sarin; Recruiting ➔ Active, not recruiting; N=30 ➔ 40

Clinical • Enrollment change • Enrollment closed • Oncology • Squamous Cell Carcinoma

Topical Remetinostat in Treating Patient With Cutaneous Basal Cell Cancer (clinicaltrials.gov) - P2; N=30; Active, not recruiting; Sponsor: Kavita Sarin; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Basal Cell Carcinoma • Oncology • STAT3

TetraLogic: Q2 2015 Results (TetraLogic) - Anticipated data from P2 trial (NCT02213861) in early stage cutaneous T-cell lymphoma at the end of 2015

Anticipated P2 data • Oncology

"Medivir delays start of Phase III remetinostat study amid FDA discussions https://t.co/eCPFaXHyJ6 #pharma @medivir @US_FDA" (@ThePharmaLetter)

P3 data

TetraLogic announces pricing of $47 million offering of convertible notes (TetraLogic Press Release) - "TetraLogic Pharmaceuticals...announced the pricing of its offering of $47 million in aggregate principal amount of its 8% Convertible Senior Notes due 2019...The Company estimates that the net proceeds from this offering will be approximately $44 million...The Company intends to use the net proceeds from this offering to finance clinical and preclinical development activities for birinapant and suberohydroxamic acid phenyl ester (SHAPE)...The offering is expected to close on June 23, 2014, subject to customary closing conditions."

Pricing • Oncology

Corporate presentation - October 2014 (TetraLogic Press Release) - "Phase 2 clinical trial with SHAPE (suberohydroxamic acid phenyl ester) in early‐stage CTCL in 4Q14"

Anticipated new P2 trial • Hematological Malignancies • Oncology

TetraLogic: Clinical Trial Update (TetraLogic) - Anticipated final results from P2 trial (NCT02213861) for CTCL in mid-2016

Anticipated P2 data • Non-Hodgkin’s Lymphoma • Oncology

TetraLogic: Oppenheimer Healthcare Conference (TetraLogic) - “Results: Four subjects (~27%) demonstrated PRs by 50% reduction in CAILS score from baseline at Days 28 or 42, Subjects on placebo demonstrated no significant improvements, No significant safety events observed: no SAEs, no discontinuations, no DLTs, no systemic sequelae (AEs: mild skin burning, erythema)“ 

P1 data • Oncology

Tolerability and encouraging clinical activity of SHP-141, a topical skin-restricted HDAC inhibitor, in a phase 1B study in cutaneous T-cell lymphoma (TetraLogic Press Release) - P1b, N=18; Sponsor: TetraLogic Pharmaceuticals; NCT01433731; "SHP-141 demonstrates excellent tolerability through 28-days of dosing; SHP-141 has promising early efficacy even with dosing limited to 28 days. Clinical response was maintained in some patient at 2-weeks post dosing; SHP-141 has evidence for local HDACi activity using a novel skin-based IHC assay; At Day 42 40% (6/15) were PRs or trending towards a PR."

P1 data • Oncology

TetraLogic: Annual Report 2015 (TetraLogic) - Anticipated composition of matter patent expiry in 2028

Anticipated patent expiry • Oncology

TetraLogic: Clinical Trial Update (TetraLogic) - "CAILS ORR at 6 months 24%; similar to that seen in phase 1 study, despite 6 months of therapy. Best CAILS response at any time point 35%"; "mSWAT ORR at 6 months 32%; best mSWAT response at any time point 41%"; "Adverse event profile tolerable; similar to that seen in phase 1. Skin events remain predominant (only) AE of interest"; "Improvement in pruritus by VAS in 38% of patients at any time point, and 80% in patients considered clinically pruritic"

P2 data • Non-Hodgkin’s Lymphoma • Oncology