Selvita: Corporate Split Going To Plan

The EHA in June 2019. As the Phase I/II study is still enrolling patients, no data have been released so far and the conference presentations focused on the design of the study, the rationale and the enrolment progress. Menarini indicated the trial will be expanded to involve approximately 40 centres in the US and Europe (until now only five centres were active, located exclusively in the US).

SEL120

Following the out-licensing of SEL24, SEL120, a selective CDK8 inhibitor, is the most advanced asset being developed by Selvita. The FDA approved an investigational new drug (IND) application in March 2019 in patients with AML or high-risk myelodysplastic syndrome. The first-in-human Phase Ib study with SEL120 is ongoing, with the first patient dosed in early September 2019 at an investigation site in the US. In total five sites are planned to be activated in the US by end of this year. Preliminary interim data will be shared by the end of 2020 and will include patients who complete the treatment before Q320. The initial focus on haematological malignancies is supported by the Leukemia and Lymphoma Society (LLS) and Selvita has received US$1.5m in research funding in total since the collaboration was established in August 2017. Selvita is also evaluating the potential of SEL120 in other haematological malignancies, including lymphomas, and in solid tumours. The company also plans preclinical combination studies of SEL120 with a number of other cancer treatment agents, such as targeted therapies, chemotherapy and checkpoint inhibitors (CPIs).

Discovery and preclinical projects

Immunooncology & immunometabolism platform

The most advanced disclosed asset within the Immunooncology & immunometabolism platform is a best-in-class dual A2A/A2B receptors antagonist. The targets belong to the so-called adenosine pathway and adenosine is one of the major microenvironmental agents that allows tumour to avoid recognition by the immune system. Selvita’s compound is highly active (picomolar activity range). In the in vivo studies presented at this year’s AACR conference in April, it demonstrated >90% tumour growth inhibition in combination with a checkpoint inhibitor (anti-CTLA4) in a CT26 syngeneic mouse model. In another melanoma mouse model (B16-F10), where the animals are completely resistant to checkpoint inhibitor (anti-PD-1) treatment, the addition of Selvita’s A2A/A2B antagonist also demonstrated significant tumour growth inhibition. These findings support the strong rationale for the synergistic potential of combinations with checkpoint inhibitors. Selvita expects to select the drug candidate and start preclinical studies in Q419.

The second most advanced project is focused on discovering small molecule, direct STING agonists. STING receptor is a known mediator of the immune system, which when activated induces the expression of type I interferon and other T-cell recruitment factors. This results in the activation of dendritic cells, which act as antigen-presenting cells. The ultimate outcome is the specific immune response with ‘trained’ CD8+ T-cells attacking the cancer. The clinical opportunity for STING agonists is also combinations with CPIs, where the STING agonist can act as a primer increasing the effectiveness of CPIs or helping to overcome the resistance. Selvita aims to select a clinical drug candidate by the end of 2020.

Synthetic lethality platform

The disclosed targets within the Synthetic lethality platform include BRM/SMARCA2. In malignant cells with the mutated SMARCA4 gene, non-mutated SMARCA2 becomes essential. Therefore the inhibition of SMARCA2 causes cell death if there is an oncogenic mutation in the SMARCA4 gene. This concept of a ‘biological genetic flaw’ complemented by an intervention with a drug, which results in cell death, is known as synthetic lethality. This approach is very specific and potentially offers a good safety profile. Selvita is developing a first-in-class, selective SMARCA2 small molecule inhibitor and the available key data were reviewed in our last outlook report . When it comes to market opportunity, the non-small cell lung cancer (NSCLC) patient population could be the first clearly defined target as SMARCA4 is mutated in around 6–8% of cases. Targets of the other projects in synthetic lethality platform remain undisclosed.

Other projects

Other earlier-stage projects include an SHMT2 inhibitor (cancer metabolism one-carbon pathway), an HPK1 inhibitor (TCR/TLR pathway) and projects in synthetic lethality. Little information has been released from these projects for competitive reasons. We expect these early-stage projects will ‘feed’ the preclinical and clinical pipeline following the corporate split and as the lead discovery and clinical projects progress.

Financials

Selvita reported total H119 revenues of PLN62.7m (up 24% y-o-y), of which commercial revenues were PLN43.5m (up 17% y-o-y) and subsidies were PLN18.6m (up 44% y-o-y). The substantial increase in the latter is a result of the initiation of new innovative R&D projects. The updated order backlog was PLN116.3m in September 2019 (up 19% year-on-year).

The operating loss was PLN16.4m in H119 vs PLN2.1m in H118, reflecting more intensive R&D (Selvita’s R&D business segment). Selvita’s CRO business segment maintained a similar operating margin of 12% (14% in H118) mainly due to preparations for the corporate split and an increase in depreciation and amortisation following capital investments made in this segment in 2018. Selvita booked PLN8.9m in depreciation in H119 compared to PLN3.6m in H118. The increase was also a result of IFRS 16 changes to lease accounting. Depreciation was the only estimate we have adjusted in our model (Exhibit 5). Selvita reported cash and cash equivalents of PLN111.3m at end-H119 and PLN3.8m in debt.

Valuation

Our pre-split valuation of Selvita is somewhat higher at PLN1.46bn or PLN91.5/share, vs PLN1.34bn or PLN83.9/share previously. The CRO business now corresponds to 36% (DCF) of the total valuation, oncology drug development 57% (rNPV) and net cash 7%. The valuation upgrade was mainly a result of the revision of our rNPVs associated with the R&D assets:

For SEL120, which is now a clinical-stage asset, we have increased the probability of success to 15% from 10% following the initiation of the Phase Ib study.

For the A2A/A2B antagonist project, we have increased the probability of success to 5% from 2%. This project has made consistent progress and is now close to the IND-enabling studies.

For SEL24, we keep the probability of success at 15%, which is typical for Phase I assets. However, we find the update from partner Menarini, which will expand the number of centres enrolling patients from five to 40, particularly encouraging. This will substantially increase the rate of spending for the trial, so shows commitment from Menarini.

Overall, we maintain our valuation approach and assumptions discussed in detail in our last outlook report . We use risk-adjusted NPV models with a discount rate of 12.5% for Selvita’s R&D projects at various stages. Separately, we use DCF-based calculations with a discount rate of 10% to value the core drug discovery services business and research collaborations.

Newsflow over the next 12 months includes:

one new pre-clinical candidate selected from the internal discovery projects (Q419);

completion of the corporate split (early Q419);

SEL24 data from Phase I part (dose escalation) of the ongoing Phase I/II study (timing depends on Menarini); and

SEL120 interim data from the Phase Ib study (2020).