Sareum Regulatory News (SAR)

This announcement contains inside information for the purposes of Article 7 of regulation 596/2014

Sareum Holdings PLC

("Sareum" or the "Company")

Portfolio Update

Sareum Holdings plc (AIM: SAR), the specialist small molecule drug development business, follows the Company's recent announcements on SRA737 with an update on other developments within its active preclinical portfolio.

The Company's active development portfolio comprises candidates being developed internally (SDC-1801 and SDC-1802) and a partnered programme (SRA737) that is out-licensed to Sierra Oncology.

These potent and selective small molecules target important mechanisms in cancer and autoimmune diseases and provide potentially high-value opportunities to develop new therapies for patients.  

Selective TYK2/JAK1 Inhibitors in Autoimmune Diseases and Cancer

Sareum's internal programmes focus on distinct dual tyrosine kinase 2 (TYK2) /Janus kinase 1 (JAK1) inhibitors, which are progressing through preclinical development as therapies for autoimmune diseases (SDC-1801) and cancers (SDC-1802). The Company is targeting first-in-human clinical trials in 2020.

Both Sareum programmes have progressed well since candidate nomination in September 2018, building on the compelling efficacy seen in disease models, the potential for once-daily oral dosing and good early safety profiles. Data arising from some of this work are being prepared for submission to a peer-reviewed publication and a conference presentation.

Sareum's recent activities have focused on toxicology studies designed to gain insight to the maximum-tolerated doses (MTD) of SDC-1801 and SDC-1802 in rodents. SDC-1801 is further advanced and currently demonstrating excellent tolerability with doses up to 30 times the level that gave good responses in efficacy studies; an MTD has yet to be reached.

Multiple dose-finding studies are now ongoing to identify doses to use in specific toxicology studies, which are intended to form part of the applications for initial human trials. Additional research to refine the clinical plans, including prioritisation of potential target indications, is continuing.

In addition, the Company has been exploring robust manufacturing routes to produce each candidate for preclinical and clinical studies. Such a route has been developed for SDC-1801 and activities continue to confirm a route of synthesis for SDC-1802.

Dr Tim Mitchell, CEO of Sareum Holdings, commented: "We believe there is a clear opportunity to generate significant value for our shareholders over the next 12 months, given recent progress with both our clinical and preclinical programmes.

"The potential for our two preclinical TYK2/JAK1 inhibitors in autoimmune diseases and cancer is gaining increasing clinical validation and we are convinced that SDC-1801 and SDC-1802 represent strong and well-differentiated candidates to address diseases within these areas. We are focused on advancing these exciting preclinical candidates towards human trials as quickly as possible, aiming for first-in-man studies to begin in 2020.

"With respect to SRA737, the Phase 1/2 data that were presented at the recent ASCO meeting by Sierra Oncology give us increasing confidence in its potential to become an attractive new therapeutic option for cancer patients. Sierra has proposed a registration-intent Phase 2 trial as a route to market in anogenital cancers for this exciting prospect, with potential for accelerated approval and payments due to Sareum linked to the achievement of certain milestones. Registration-intent Phase 2 trials represent an efficient approach to accelerate time to market for drugs intended to treat life-threatening diseases where no effective treatment exists.

"Anogenital cancer represents a distinct and substantial market opportunity as there are currently no 2nd-line therapies approved once chemotherapy becomes ineffective and these patients have a very poor life expectancy. The striking anti-tumour activity reported in the SRA737+Low Dose Gemcitabine (LDG) trial is a notable result, considering the advanced state of the cancers and the extent of previous treatments that patients received.

"Both Sierra and Sareum believe that SRA737 is competitively positioned as potentially one of the leading clinical assets in its class. In both trials, the treatments were safe and well tolerated, with the majority of adverse events being only mild or moderate. The safety profiles of SRA737 monotherapy and SRA737+LDG were markedly superior to those of recently discontinued molecules from Lilly (prexasertib) and Genentech/Roche (GDC-0575).

"Additionally, we continue to seek other opportunities to which the Company could add value and grow the business, and our recently expanded Board is instrumental in this search."

For further information, please contact: 

Notes for editors: 

Sareum is a specialist drug development company delivering targeted small molecule therapeutics, to improve the treatment of cancer and autoimmune disease. The Company generates value through licensing its candidates to international pharmaceutical and biotechnology companies at the preclinical or early clinical trials stage.

Sareum's leading clinical-stage programme, SRA737, a novel Checkpoint kinase 1 (Chk1) inhibitor licensed to NASDAQ-listed Sierra Oncology, is in Phase 2 clinical trials targeting multiple advanced cancers. The key role of Chk1 in cancer cell replication and DNA damage repair suggests that SRA737 may have broad application as a targeted therapy in combination with other oncology and immune-oncology drugs in genetically defined patients.

SRA737 was discovered and initially developed by scientists at The Institute of Cancer Research, London, UK in collaboration with Sareum, and with funding from Cancer Research UK. SRA737 was licensed to Sierra Oncology for up to $328.5 million plus royalties by our co-investment partner, CRT Pioneer Fund. Sareum is eligible to receive up to $88 million in milestone payments, plus sales royalties as SRA737 advances.

Notable highlights from the Phase 1/2 preliminary results reported by Sierra at ASCO were:

SRA737 + low dose gemcitabine (LDG) combination

· Striking anti-tumour activity was observed in patients with anogenital cancer, including examples where metastatic disease was cleared from liver and lung.

· Tumour size decreased by more than a third in 30% of the evaluable anogenital cancer patients and a further 30% had durable stable disease.

· Sierra outlined a potential route to market for SRA737+LDG in anogenital cancer via a registration-intent Phase 2 trial.

SAR737 monotherapy

As expected, high-grade serous ovarian cancers (HGSOC) appeared to be the most sensitive tumour to SRA737, with the disease being controlled (stable disease) in 54% of evaluable patients.

Sareum is also advancing internal programmes focused on distinct dual tyrosine kinase 2 (TYK2) /Janus kinase 1 (JAK1) inhibitors through preclinical development as therapies for autoimmune diseases (SDC-1801) and cancers (SDC-1802). TYK2 and JAK1 have roles in pro-inflammatory responses in autoimmune diseases (e.g. psoriasis, rheumatoid arthritis, inflammatory bowel diseases and lupus) and tumour cell proliferation in certain cancers (e.g. T-cell acute lymphoblastic leukaemia and some solid tumours). The Company is targeting first human clinical trials in each indication in 2020.

The Company also has an Aurora+FLT3 inhibitor targeting haematological cancers, which is at the preclinical development stage.

Sareum Holdings plc is listed on the AIM market of the London Stock Exchange, trading under the ticker SAR. For further information, please visit www.sareum.co.uk

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